RESUMEN
Lung adenocarcinoma (LUAD) is the dominant histotype of non-small cell lung cancer. Panoptosis, a comprehensive form of programmed cell death, is central to carcinogenesis. In this study, the expression of PANoptosis-related genes (PRGs) and their impact on the development, prognosis, tumor microenvironment, and treatment response of patients with lung adenocarcinoma (LUAD) were systematically evaluated. PRGs were selected from The Cancer Genome Atlas database and Genecards dataset using differential expression analysis. The signature of included PRGs was identified using univariate Cox regression analysis and LASSO regression analysis. Additionally, a nomogram was developed that includes signature and clinical information. Kaplan-Meier survival analysis and receiver operating characteristic curves were used to assess the predictive validity of these risk models. Finally, functional analysis of the selected PRGs in signature and analysis of immune landscape were also performed. Preliminary identification of 10 genes related to PANoptosis has significant implications for prognosis. Subsequently, seven related genes were integrated to classify LUAD patients into different survival risk groups. The prognostic risk score generated from the signature and the TNM stage were as independent prognostic factors and were utilized in creating a nomogram plot. Both the features and the nomogram plot showed accurate performance in predicting the overall survival of LUAD patients. The PRGs were enriched in several biological functions and pathways, and stratified studies were conducted on the differences in immune landscape between high-risk and low-risk groups based on their characteristics. Ultimately, our evaluation focused on the differences in drug treatment efficacy between the high-risk and low-risk groups, providing a foundation for future research directions. Potential associations between PRGs and patient prognosis in LUAD have been identified in this study. Potential biomarkers for clinical application could be considered for the prognostic predictors identified in this study.
Asunto(s)
Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/mortalidad , Adenocarcinoma del Pulmón/terapia , Adenocarcinoma del Pulmón/diagnóstico , Pronóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamiento farmacológico , Biomarcadores de Tumor/genética , Masculino , Femenino , Nomogramas , Microambiente Tumoral/genética , Perfilación de la Expresión Génica , Estimación de Kaplan-Meier , Curva ROC , Persona de Mediana EdadRESUMEN
OBJECTIVE: To intelligently evaluate the invasiveness of pure ground-glass nodules with multiple classifications using deep learning. METHODS: pGGNs in 1136 patients were pathologically confirmed as lung precursor lesions [atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS)], minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IAC). Four different models [EfficientNet-b0 2D, dual-head ResNet_3D, a 3D model combining three features (3D_3F), and a 3D model combining 19 features (3D_19F)] were constructed to evaluate the invasiveness of pGGNs using the EfficientNet and ResNet networks. The Obuchowski index was used to evaluate the differences in diagnostic efficiency among the four models. RESULTS: The patients with pGGNs (360 men, 776 women; mean age, 54.63 ± 12.36 years) included 235 cases of AAH + AIS, 332 cases of MIA, and 569 cases of IAC. In the validation group, the areas under the curve in detecting the invasiveness of pGGNs as a three-category classification (AAH + AIS, MIA, IAC) were 0.8008, 0.8090, 0.8165, and 0.8158 for EfficientNet-b0 2D, dual-head ResNet_3D, 3D_3F, and 3D_19F, respectively, whereas the accuracies were 0.6422, 0.6158, 0.651, and 0.6364, respectively. The Obuchowski index revealed no significant differences in the diagnostic performance of the four models. CONCLUSIONS: The dual-head ResNet_3D_3F model had the highest diagnostic efficiency for evaluating the invasiveness of pGGNs in the four models.
Asunto(s)
Neoplasias Pulmonares , Invasividad Neoplásica , Humanos , Persona de Mediana Edad , Femenino , Masculino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico , Anciano , Adulto , Aprendizaje Profundo , Adenocarcinoma in Situ/patología , Lesiones Precancerosas/patología , Lesiones Precancerosas/diagnóstico , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/diagnóstico , Nódulos Pulmonares Múltiples/patología , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/diagnóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Qi deficiency and phlegm dampness (QPD) is one of the most common traditional Chinese medicine (TCM) syndromes in lung adenocarcinoma (LUAD). This study aimed to identify syndrome-specific biomarkers for LUAD with QPD syndrome. METHODS: Peripheral blood mononuclear cells (PBMCs) from LUAD patients with QPD, LUAD patients with non-QPD (N-QPD), and healthy control (H) were collected and analyzed with RNA-seq to identify differentially expressed genes (DEGs). The area under the receiver operator characteristic curve (AUC) of each DEG was calculated, and the top 10 highest AUC DEGs were validated by qRT-PCR. Logistic regression analysis was used to develop a diagnostic model evaluated with AUC. RESULTS: A total of 135 individuals were enrolled in this study (training set: 15 QPD, 15 N-QPD, 15 H; validation set: 30 QPD, 30 N-QPD, 30 H). A total of 1480 DEGs were identified between QPD and N-QPD. The qRT-PCR results showed that the expression of DDR2 was downregulated, and PPARG was upregulated, which was in line with the finding of the training set. We developed a diagnostic model with these two genes. The AUC of the diagnostic model in the training cohort and validation cohort was 0.891 and 0.777, respectively. CONCLUSIONS: We identified the two genes (DDR2 and PPARG) as syndrome-specific biomarkers for LUAD with QPD syndrome and developed a novel diagnostic model, which may help to improve the accuracy and sensibility of clinical diagnosis and provide a new target for natural drug treatment of LUAD.
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Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Neoplasias Pulmonares , Medicina Tradicional China , Humanos , Masculino , Femenino , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Medicina Tradicional China/métodos , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Anciano , Qi , Leucocitos Mononucleares/metabolismo , Curva ROC , Estudios de Casos y ControlesRESUMEN
The invasive mucinous adenocarcinoma of the lungs (LIMA) is an uncommon histological subtype of the mucinous adenocarcinoma. In this article, we present the case of a patient with a very high cardiovascular risk profile, diagnosed with LIMA, pericardial tamponade due to secondary dissemination, and pulmonary embolism, whose management rouses many challenges. Despite receiving the correct anticoagulant and antiaggregant therapy, our patient developed repeated acute major cardiovascular events leading to a fatal outcome. To gather additional information on LIMA and the above cluster of pathologies, we performed the first research of the international medical literature for scientific articles published in the last eight years on PubMed, ResearchGate, Clarivate, and Google Scholar. As the first literature research failed to identify any case similar to our patient, we performed a second study of the same databases for subjects with lung adenocarcinoma instead of LIMA and the same comorbidities, and we found 10 cases. LIMA is a less frequent type of adenocarcinoma, with polymorphic radiologic appearances on the chest computed tomography, frequently mimicking pneumonia, and thus delaying the diagnosis and therapy. It has a worse prognosis and higher mortality than the common adenocarcinoma, but information on its secondary dissemination and complications is still required.
Asunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma Mucinoso , Taponamiento Cardíaco , Neoplasias Pulmonares , Embolia Pulmonar , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma del Pulmón/complicaciones , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/patología , Adenocarcinoma Mucinoso/complicaciones , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/patología , Taponamiento Cardíaco/diagnóstico , Taponamiento Cardíaco/etiología , Resultado Fatal , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/complicaciones , Embolia Pulmonar/etiología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Lung adenocarcinoma (LUAD) has been observed to have significant sex differences in incidence, prognosis, and response to therapy. However, the molecular mechanisms responsible for these disparities have not been investigated extensively. METHODS: Sample-specific gene regulatory network methods were used to analyze RNA sequencing data from non-cancerous human lung samples from The Genotype Tissue Expression Project (GTEx) and lung adenocarcinoma primary tumor samples from The Cancer Genome Atlas (TCGA); results were validated on independent data. RESULTS: We found that genes associated with key biological pathways including cell proliferation, immune response and drug metabolism are differentially regulated between males and females in both healthy lung tissue and tumor, and that these regulatory differences are further perturbed by tobacco smoking. We also discovered significant sex bias in transcription factor targeting patterns of clinically actionable oncogenes and tumor suppressor genes, including AKT2 and KRAS. Using differentially regulated genes between healthy and tumor samples in conjunction with a drug repurposing tool, we identified several small-molecule drugs that might have sex-biased efficacy as cancer therapeutics and further validated this observation using an independent cell line database. CONCLUSIONS: These findings underscore the importance of including sex as a biological variable and considering gene regulatory processes in developing strategies for disease prevention and management.
Lung adenocarcinoma (LUAD) is a disease that affects males and females differently. Biological sex not only influences chances of developing the disease, but also how the disease progresses and how effective various therapies may be. We analyzed sex-specific gene regulatory networks consisting of transcription factors and the genes they regulate in both healthy lung tissue and in LUAD and identified sex-biased differences. We found that genes associated with cell proliferation, immune response, and drug metabolism are differentially targeted by transcription factors between males and females. We also found that several genes that are drug targets in LUAD, are also regulated differently between males and females. Importantly, these differences are also influenced by an individual's smoking history. Extending our analysis using a drug repurposing tool, we found candidate drugs with evidence that they might work better for one sex or the other. These results demonstrate that considering the differences in gene regulation between males and females will be essential if we are to develop precision medicine strategies for preventing and treating LUAD.
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Adenocarcinoma del Pulmón , Redes Reguladoras de Genes , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/terapia , Factores Sexuales , Regulación Neoplásica de la Expresión Génica/genética , Pulmón/metabolismo , Fumar Tabaco/efectos adversos , Pronóstico , Inmunoterapia , Terapia Molecular Dirigida , Línea Celular Tumoral , Humanos , Masculino , Femenino , Descubrimiento de DrogasRESUMEN
Pulmonary cryptococcosis (PC) is a common opportunistic fungal infection caused by Cryptococcus neoformans or Cryptococcus gattii. PC primarily invades the respiratory system, followed by the central nervous system. Few clinical reports have examined the coexistence of PC and lung cancer. This study reports the case of a 54-year-old immunocompetent PC patient with lung adenocarcinoma. Chest CT revealed multiple nodules in the right lung, with the largest nodule located in the dorsal segment of the right lower lobe. 18 FFDG positron emission tomography-computed tomography (PET-CT) revealed elevated glucose metabolism in the dorsal segment of the right lower lobe, which suggested lung cancer. The metabolism level of the nodule in the basal segment of the right lower lobe and the anterior segment of the right upper lobe was not abnormally increased, but the possibility of a malignant tumour could not be excluded. The pulmonary nodules in the dorsal segment and the basal segment of the right lower lobe were simultaneously resected via video-assisted thoracic surgery (VATS), and the final histopathology revealed primary lung adenocarcinoma and pulmonary cryptococcal infection, respectively. After surgery, antifungal treatment was administered for 3 months. Over the 3-year follow-up, contrast-enhanced computed tomography (CT) revealed no recurrence of either disease. This case study highlights the possibility of dualism in the diagnosis of multiple pulmonary nodules on chest CT, such as the coexistence of lung cancer and PC. Surgical resection is recommended for micronodules that are not easy to diagnose via needle biopsy; in addition, early diagnosis and treatment are helpful for ensuring a good prognosis. This paper reports the clinical diagnosis and treatment of one patient with pulmonary cryptococcal infection of the right lung complicated with lung adenocarcinoma, including 3 years of follow-up, providing a reference for clinical practice.
Asunto(s)
Adenocarcinoma del Pulmón , Criptococosis , Enfermedades Pulmonares Fúngicas , Neoplasias Pulmonares , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Persona de Mediana Edad , Adenocarcinoma del Pulmón/complicaciones , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/cirugía , Antifúngicos/administración & dosificación , Criptococosis/complicaciones , Criptococosis/diagnóstico , Criptococosis/patología , Criptococosis/terapia , Pulmón/diagnóstico por imagen , Pulmón/microbiología , Pulmón/patología , Pulmón/cirugía , Enfermedades Pulmonares Fúngicas/complicaciones , Enfermedades Pulmonares Fúngicas/diagnóstico , Enfermedades Pulmonares Fúngicas/patología , Enfermedades Pulmonares Fúngicas/terapia , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Cirugía Torácica Asistida por Video , Tomografía Computarizada por Rayos XRESUMEN
Lung adenocarcinoma is the most common primary lung cancer seen in the world, and identifying genetic markers is essential for predicting the prognosis of lung adenocarcinoma and improving treatment outcomes. It is well known that alterations in circadian rhythms are associated with a higher risk of cancer. Moreover, circadian rhythms play a regulatory role in the human body. Therefore, studying the changes in circadian rhythms in cancer patients is crucial for optimizing treatment. The gene expression data and clinical data were sourced from TCGA database, and we identified the circadian clock-related genes. We used the obtained TCGA-LUAD data set to build the model, and the other 647 lung adenocarcinoma patients' data were collected from two GEO data sets for external verification. A risk score model for circadian clock-related genes was constructed, based on the identification of 8 genetically significant genes. Based on ROC analyses, the risk model demonstrated a high level of accuracy in predicting the overall survival times of lung adenocarcinoma patients in training folds, as well as external data sets. This study has successfully constructed a risk model for lung adenocarcinoma prognosis, utilizing circadian rhythm as its foundation. This model demonstrates a dependable capacity to forecast the outcome of the disease, which can further guide the relevant mechanism of lung adenocarcinoma and combine behavioral therapy with treatment to optimize treatment decision-making.
Asunto(s)
Adenocarcinoma del Pulmón , Relojes Circadianos , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/patología , Pronóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Relojes Circadianos/genética , Femenino , Masculino , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Ritmo Circadiano/genética , Persona de Mediana Edad , Bases de Datos GenéticasRESUMEN
The fascinating role of SPRR3 in various malignant tumors has prompted extensive research to unravel its expression patterns and prognostic significance. To comprehensively investigate SPRR3, we leveraged multiple datasets containing invaluable biomedical information, specifically focusing on the comparative analysis of SPRR3 gene expression levels across different cancer types. Meticulous examination of lung adenocarcinoma allowed us to delve deeper into the correlation between SPRR3 expression and its molecular biological functions. Our comprehensive analysis encompassed 33 malignant tumors, and the results unveiled significant differential expression of SPRR3 across a range of malignancies. Moreover, this aberrant expression of SPRR3 was observed to be closely associated with poorer prognosis in these malignant tumors. Notably, our investigation also unearthed a compelling link between SPRR3 and immune infiltrating cells in lung adenocarcinoma. The utilization of receiver operating characteristic (ROC) curves and survival curves in our study illustrated the immense potential of SPRR3 as a highly accurate predictor of cancer. These findings further emphasize the possibility of SPRR3 serving as a promising diagnostic and prognostic biomarker for a diverse array of cancers.
Asunto(s)
Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Pronóstico , Biomarcadores de Tumor/genética , Curva ROC , Proteínas Ricas en Prolina del Estrato Córneo/genética , Proteínas Ricas en Prolina del Estrato Córneo/metabolismoRESUMEN
The deregulation of amino acid and polyamine metabolism is a hallmark of malignancy that regulates cancer cell proliferation, angiogenesis, and invasion. A sensitive mass spectrometry method was developed to simultaneously quantify 10 cancer-associated metabolites in pleural effusion cells for the diagnosis of malignancy and to complement conventional pleural cytology. Analytes were detected by high-performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) using C8-reversed-phase HPLC for separation and sequential window acquisition of all theoretical fragment ion spectra (SWATH) acquisition for obtaining high-resolution quantitative MS/MS chromatograms. This method was validated and applied to pleural effusion cells from patients with lung adenocarcinoma (LUAD, n = 48) and those from benign controls (n = 23). The range of the above metabolites was 2-200â¯ng/mL for proline, aspartate, ornithine, creatine, glutamine, glutamate, arginine, citrulline, and spermine and 10-1000â¯ng/mL for putrescine. The intra-assay and inter-assay coefficient of variation was below 13.70â¯% for all analytes. The joint detection of these metabolites in pleural effusion cells achieved a clinical sensitivity of 75.0â¯% and specificity of 95.7â¯% differentiating LUAD patients from benign controls. This assay enabled the detection of 10 cancer-associated metabolites in pleural effusion cells, and the increased concentration of these metabolites was correlated with the presence of LUAD.
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Adenocarcinoma del Pulmón , Aminoácidos , Neoplasias Pulmonares , Poliaminas , Espectrometría de Masas en Tándem , Humanos , Cromatografía Líquida de Alta Presión/métodos , Poliaminas/análisis , Poliaminas/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/diagnóstico , Aminoácidos/análisis , Aminoácidos/metabolismo , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/diagnóstico , Masculino , Espectrometría de Masas en Tándem/métodos , Femenino , Persona de Mediana Edad , Anciano , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/diagnóstico , Sensibilidad y Especificidad , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Colorectal (CRC) and lung adenocarcinoma share many genetic and pathological similarities. A circulating tumor DNA (ctDNA) test for CRC may also be useful for detection of lung adenocarcinoma. This study determined if a methylated BCAT1/IKZF1 ctDNA test for CRC can be used for detection of lung adenocarcinoma. PATIENTS AND METHODS: Circulating cell free DNA (ccfDNA) was extracted from plasma collected prospectively from healthy controls, patients in remission from CRC, patients with lung adenocarcinoma, and patients with isolated metastatic CRC lung lesions. Plasma ccfDNA was bisulfite converted and assessed for methylated BCAT1/IKZF1 by quantitative real-time PCR. Comparisons between the different patient groups for a positive ctDNA test (BCAT1 and/or IKZF1) and ctDNA levels (% of total ccfDNA), as well as any associations with clinicopathological and demographic features, were assessed. RESULTS: Methylated BCAT1/IKZF1 ctDNA was detected in 18/39 (46.2 %) patients with lung adenocarcinoma, which was significantly (p < 0.001) higher compared to healthy controls (49/606; 8.1 %) and patients in remission from CRC (22/171, 12.9 %). Patients with stage III/IV lung adenocarcinoma had higher BCAT1/IKZF1 ctDNA positivity compared to stage I/II cases (68.2 % vs 17.7 %, p < 0.01), where a significantly higher proportion tested positive for methylated IKZF1 ctDNA alone (54.6 % vs 5.9 %, p < 0.001). There was no difference in BCAT1/IKZF1 ctDNA test positivity between patients with stage IV primary lung adenocarcinoma (n = 17) compared to lung-metastasising CRC cases (n = 17; 70.6 % v 64.3 %). CONCLUSION: A ctDNA test measuring methylated BCAT1/IKZF1 can sensitively detect lung adenocarcinoma and may be a promising aid for detection of advanced disease. CLINICAL TRIAL REGISTRATIONS: Australian and New Zealand Clinical Trials Registry, www.anzctr.org.au, ACTRN12616001138471, ACTRN12611000318987.
Asunto(s)
Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Metilación de ADN , Factor de Transcripción Ikaros , Neoplasias Pulmonares , Humanos , Factor de Transcripción Ikaros/genética , Masculino , Femenino , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/sangre , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/diagnóstico , Persona de Mediana Edad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Anciano , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Estudios Prospectivos , Adulto , Estudios de Casos y Controles , TransaminasasRESUMEN
OBJECTIVE: To establish a prediction model of lung cancer classification by computed tomography (CT) radiomics with the serum tumor markers (STM) of lung cancer. MATERIALS AND METHODS: Two-hundred NSCLC patients were enrolled in our study. Clinical data including age, sex, and STM (squamous cell carcinoma [SCC], neuron-specific enolase [NSE], carcinoembryonic antigen [CEA], pro-gastrin-releasing peptide [PRO-GRP], and cytokeratin 19 fragment [cYFRA21-1]) were collected. A radiomics signature was generated from the training set using the least absolute shrinkage and selection operator (LASSO) algorithm. The risk factors were identified using multivariate logistic regression analysis, and a radiomics nomogram based on the radiomics signature and clinical features was constructed. The capability of the nomogram was evaluated using the training set and validated using the validation set. A correction curve and the Hosmer-Lemeshow test were used to evaluate the predictive performance of the radiomics model for the training and test sets. RESULTS: Twenty-nine of 1234 radiomics parameters were screened as important factors for establishing the radiomics model. The training (area under the curve [AUC] = 0.925; 95% confidence interval [CI]: 0.885-0.966) and validation sets (AUC = 0.921; 95% CI: 0.854-0.989) showed that the CT radiomics signature, combined with STM, accurately predicted lung squamous cell carcinoma and lung adenocarcinoma. Moreover, the logistic regression model showed good performance based on the Hosmer-Lemeshow test in the training (P = 0.954) and test sets (P = 0.340). Good calibration curve consistency also indicated the good performance of the nomogram. CONCLUSION: The combination of the CT radiomics signature and lung cancer STM performed well for the pathological classification of NSCLC. Compared with the radiomics signature method, the nomogram based on the radiomics signature and clinical factors had better performance for the differential diagnosis of NSCLC.
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Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Nomogramas , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Tomografía Computarizada por Rayos X/métodos , Biomarcadores de Tumor/sangre , Persona de Mediana Edad , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Anciano , Adenocarcinoma del Pulmón/sangre , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/diagnóstico , Adulto , Curva ROC , Queratina-19/sangre , RadiómicaRESUMEN
Untargeted metabolomic analysis using mass spectrometry provides comprehensive metabolic profiling, but its medical application faces challenges of complex data processing, high inter-batch variability, and unidentified metabolites. Here, we present DeepMSProfiler, an explainable deep-learning-based method, enabling end-to-end analysis on raw metabolic signals with output of high accuracy and reliability. Using cross-hospital 859 human serum samples from lung adenocarcinoma, benign lung nodules, and healthy individuals, DeepMSProfiler successfully differentiates the metabolomic profiles of different groups (AUC 0.99) and detects early-stage lung adenocarcinoma (accuracy 0.961). Model flow and ablation experiments demonstrate that DeepMSProfiler overcomes inter-hospital variability and effects of unknown metabolites signals. Our ensemble strategy removes background-category phenomena in multi-classification deep-learning models, and the novel interpretability enables direct access to disease-related metabolite-protein networks. Further applying to lipid metabolomic data unveils correlations of important metabolites and proteins. Overall, DeepMSProfiler offers a straightforward and reliable method for disease diagnosis and mechanism discovery, enhancing its broad applicability.
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Aprendizaje Profundo , Neoplasias Pulmonares , Espectrometría de Masas , Metaboloma , Metabolómica , Humanos , Metabolómica/métodos , Espectrometría de Masas/métodos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/sangre , Adenocarcinoma del Pulmón/diagnóstico , Masculino , Femenino , Análisis de Datos , Reproducibilidad de los Resultados , Persona de Mediana EdadRESUMEN
INTRODUCTION AND IMPORTANCE: Lung adenocarcinoma may resemble the clinical presentation of an infectious or inflammatory lung disease. The coexistence of lung cancer, and polyserous effusions is uncommon, which may cause a diagnostic challenge. However, any polyserous effusions at a young age must always be suspicious for malignancy. CASE PRESENTATION: We report a case of 38-year-old male patient with polyserous effusions and pneumonia who was treated accordingly and showed clinical improvement with a significant reduction of pericardial and pleural effusions. Subsequent testing and a biopsy resulted in the histopathological diagnosis of an adenocarcinoma of the lung. CLINICAL DISCUSSION: Nonrecurrent polyserous effusions in lung adenocarcinoma are uncommon, and negative cytology results may not exclude malignancy due to the moderate sensitivity of pleural and pericardial fluid cytology. Clinicians should remain vigilant for false-negative results, especially in younger patients. Malignancy should not be ruled out because pleural and pericardial fluid cytology have a sensitivity of 60% and 92%, respectively. CONCLUSION: Our case highlights the diagnostic challenges posed by atypical presentations of lung adenocarcinoma and emphasizes the importance of considering malignancy in the differential diagnosis of polyserous effusions, even when initial cytology results are negative. Clarifying the rationale for this study enhances its relevance and impact.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Neumonía , Humanos , Masculino , Adulto , Diagnóstico Diferencial , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/complicaciones , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/patología , Neumonía/diagnóstico , Derrame Pericárdico/etiología , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/patología , Derrame Pleural/diagnóstico , Derrame Pleural/etiología , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Derrame Pleural Maligno/patología , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/etiología , CitologíaRESUMEN
Background: Introduction: Circular RNAs (circRNAs) have been identified as significant contributors to the development and advancement of cancer. The objective of this study was to examine the expression and clinical implications of circRNA circ_BBS9 in lung adenocarcinoma (LUAD), as well as its potential modes of action. Methods: The expression of Circ_BBS9 was examined in tissues and cell lines of LUAD through the utilization of microarray profiling, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis. In this study, we assessed the impact of circ_BBS9 on the proliferation of LUAD cells, as well as its influence on ferroptosis and tumor formation. To analyze these effects, we employed CCK-8 assays and ferroptosis assays. The identification of proteins that interact with Circ_BBS9 was achieved through the utilization of RNA pull-down and mass spectrometry techniques. A putative regulatory network comprising circ_BBS9, miR-7150, and IFIT3 was established using bioinformatics study. The investigation also encompassed the examination of the correlation between the expression of IFIT3 and the invasion of immune cells. Results: Circ_BBS9 was significantly downregulated in LUAD tissues and cell lines. Low circ_BBS9 expression correlated with poor prognosis. Functional experiments showed that circ_BBS9 overexpression inhibited LUAD cell proliferation and promoted ferroptosis in vitro and suppressed tumor growth in vivo. Mechanistically, circ_BBS9 was found to directly interact with IFIT3 and regulate its expression by acting as a sponge for miR-7150. Additionally, IFIT3 expression correlated positively with immune infiltration in LUAD. Conclusion: Circ_BBS9 has been identified as a tumor suppressor in lung adenocarcinoma (LUAD) and holds promise as a diagnostic biomarker. The potential mechanism of action involves the modulation of ferroptosis and the immunological microenvironment through direct interaction with IFIT3 and competitive binding to miR-7150. The aforementioned findings offer new perspectives on the pathophysiology of LUAD and highlight circ_BBS9 as a potentially valuable target for therapeutic interventions.
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Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Ferroptosis , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , ARN Circular , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , ARN Circular/genética , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/diagnóstico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Biomarcadores de Tumor/genética , Animales , Ratones , Ferroptosis/genética , Ferroptosis/inmunología , Línea Celular Tumoral , MicroARNs/genética , Masculino , Proliferación Celular , Femenino , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Persona de Mediana Edad , Ratones Desnudos , Péptidos y Proteínas de Señalización IntracelularRESUMEN
The objective of this study was to develop a nomogram model based on the natural progression of tumor and other radiological features to discriminate between solitary nodular pulmonary mucinous adenocarcinoma and non-mucinous adenocarcinomas. A retrospective analysis was conducted on 15,655 cases of lung adenocarcinoma diagnosed at our institution between January 2010 and June 2023. Primary nodular invasive mucinous adenocarcinomas and non-mucinous adenocarcinomas with at least two preoperative CT scans were included. These patients were randomly assigned to training and validation sets. Univariate and multivariate analyses were employed to compare tumor growth rates and clinical radiological characteristics between the two groups in the training set. A nomogram model was constructed based on the results of multivariate analysis. The diagnostic value of the model was evaluated in both the training and validation sets using calibration curves and receiver operating characteristic curves (ROC). The study included 174 patients, with 58 cases of mucinous adenocarcinoma and 116 cases of non-mucinous adenocarcinoma. The nomogram model incorporated the maximum tumor diameter, the consolidation/tumor ratio (CTR), and the specific growth rate (SGR) to generate individual scores for each patient, which were then accumulated to obtain a total score indicative of the likelihood of developing mucinous or non-mucinous adenocarcinoma. The model demonstrated excellent discriminative ability with an area under the receiver operating characteristic curve of 0.784 for the training set and 0.833 for the testing set. The nomogram model developed in this study, integrating SGR with other radiological and clinical parameters, provides a valuable and accurate tool for differentiating between solitary nodular pulmonary mucinous adenocarcinoma and non-mucinous adenocarcinomas. This prognostic model offers a robust and objective basis for personalized management of patients with pulmonary adenocarcinomas.
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Adenocarcinoma Mucinoso , Neoplasias Pulmonares , Nomogramas , Humanos , Femenino , Masculino , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico por imagen , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Nódulo Pulmonar Solitario/patología , Nódulo Pulmonar Solitario/diagnóstico , Nódulo Pulmonar Solitario/diagnóstico por imagen , Curva ROC , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adulto , Anciano de 80 o más AñosRESUMEN
BACKGROUND Guillain-Barre syndrome (GBS) is a rare immune-mediated peripheral nerve disorder. Among non-infectious factors, surgery has been identified as a potential trigger of the disease. This report presents the case of a 74-year-old man who developed GBS 15 days after a right lower lobectomy for lung adenocarcinoma. CASE REPORT We present a case of a patient who was a former smoker who underwent uniportal video-assisted (U-VATS) right lower lobectomy for localized lung adenocarcinoma. Fifteen days after surgery, he exhibited bilateral lower-limb weakness, widespread paresthesia, and postural instability. Comprehensive diagnostic workup, including clinical assessment, serological tests, cerebrospinal fluid (CSF) analysis, and nerve conduction studies (NCS), confirmed the diagnosis. Notably, CSF analysis revealed albumin-cytological dissociation, with albumin 453.2 mg/L, protein 757 mg/L, glucose 67 mg/dl, 3 white blood cells (WBC)/uL, and polymorphonucleates (PMN) 33%. NCS demonstrated motor and sensory abnormalities. Prompt administration of intravenous immunoglobulins (IVIG) 2 g/kg daily for 5 days resulted in complete recovery within 3 months. CONCLUSIONS This case emphasizes the importance of prompt recognition and management of GBS as a postoperative complication. Neurological examination, neuroimaging, and electrophysiological studies are essential for accurate diagnosis. IVIG therapy remains a cornerstone in GBS management, with favorable outcomes observed in this case. Enhanced awareness among clinicians about the potential association between surgery and GBS is vital to prevent more serious complications and ensure optimal patient management. Further research is crucial to determine the precise pathogenesis and mechanisms of GBS following lung surgery.
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Adenocarcinoma del Pulmón , Síndrome de Guillain-Barré , Neoplasias Pulmonares , Humanos , Síndrome de Guillain-Barré/etiología , Síndrome de Guillain-Barré/diagnóstico , Masculino , Anciano , Neoplasias Pulmonares/cirugía , Adenocarcinoma del Pulmón/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Adenocarcinoma/cirugía , Inmunoglobulinas Intravenosas/uso terapéutico , Cirugía Torácica Asistida por Video , Neumonectomía/efectos adversosRESUMEN
The clinical presentation, cytologic findings, radiographic findings, and postmortem assessment of a cat with primary pulmonary adenocarcinoma with multiple digital metastasis are described. An unusual shifting, waxing and waning pattern of lameness, suspected to be an early manifestation of digital metastasis before any gross lesions were visible, was documented. Initial cytologic finding of a lung nodule was equivocal for diagnosis of neoplasia despite being strongly suspicious. Palliative management was short-lived, with rapid progression culminating in widespread metastasis to multiple digits, muscles, and other organs. The diagnosis of pulmonary adenocarcinoma was confirmed via necropsy and histopathology. Key clinical message: This case report highlights that feline lung-digit syndrome is an important differential diagnosis for an acute, waxing and waning, shifting leg lameness in an older cat. This pattern of lameness should raise the index of suspicion for an underlying primary lung neoplasm, and thoracic imaging (radiographs) should be considered.
Syndrome pulmonaire-digital félin : un diagnostic différentiel des boiteries changeantes, croissantes et décroissantes chez un chatLa présentation clinique, les résultats cytologiques, les résultats radiographiques et l'évaluation post mortem d'un chat atteint d'adénocarcinome pulmonaire primaire avec métastases numériques multiples sont décrits. Un schéma inhabituel de boiterie, variable, croissante et décroissante, suspecté d'être une manifestation précoce de métastases digitales avant que des lésions macroscopiques ne soient visibles, a été documenté. La découverte cytologique initiale d'un nodule pulmonaire était équivoque pour le diagnostic de néoplasie bien qu'elle soit fortement suspecte. La prise en charge palliative a été de courte durée, avec une progression rapide aboutissant à des métastases généralisées à plusieurs doigts, muscles et autres organes. Le diagnostic d'adénocarcinome pulmonaire a été confirmé par autopsie et histopathologie.Message clinique clé :Ce rapport de cas souligne que le syndrome pulmonaire-digital félin est un diagnostic différentiel important pour une boiterie aiguë, croissante et décroissante et mobile des pattes chez un chat ágé. Ce type de boiterie devrait faire suspecter une tumeur primaire du poumon sous-jacente, et une imagerie thoracique (radiographies) devrait être envisagée.(Traduit par Dr Serge Messier).
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Adenocarcinoma , Enfermedades de los Gatos , Cojera Animal , Neoplasias Pulmonares , Gatos , Animales , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/patología , Neoplasias Pulmonares/veterinaria , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Cojera Animal/diagnóstico , Cojera Animal/etiología , Diagnóstico Diferencial , Adenocarcinoma/veterinaria , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Masculino , Síndrome , Adenocarcinoma del Pulmón/veterinaria , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/patología , FemeninoRESUMEN
BACKGROUND: Lung adenocarcinoma (LUAD) represents the most prevalent type of lung cancer. SHOX2 and RASSF1A methylation have been identified as important biomarkers for diagnosis and prognosis of lung cancer. Bronchoalveolar lavage fluid (BALF) exhibits good specificity and sensitivity in diagnosing pulmonary diseases, but its acquisition is challenging and may cause discomfort to patients. In clinical, plasma samples are more convenient to obtain than BALF; however, there is little research on the concurrent detection of SHOX2 and RASSF1A methylation in plasma. This study aims to assess the diagnostic value of a combined promoter methylation assay for SHOX2 and RASSF1A in early-stage LUAD using plasma samples. METHODS: BALF and blood samples were obtained from 36 early-stage LUAD patients, with a control group of nineteen non-tumor individuals. The promoter methylation levels of SHOX2 and RASSF1A in all subjects were assessed using the human SHOX2 and RASSF1A gene methylation kit. RESULTS: The methylation detection rate of SHOX2 and RASSF1A in plasma was 61.11%, slightly lower than that in BALF (66.7%). The Chi-square test revealed no significant difference in the methylation rate between BALF and plasma (P > 0.05). The area under the receiver operating characteristic (ROC) curve analysis for blood was 0.806 (95% CI, 0.677 to 0.900), while for BALF it was 0.781 (95% CI, 0.649 to 0.881). Additionally, we conducted an analysis on the correlation between SHOX2 and RASSF1A methylation levels in plasma with gender, age, tumor differentiation, pathologic classification, and other clinicopathological variables; however, no significant correlations were observed. CONCLUSIONS: Measurement of SHOX2 and RASSF1A methylation for early diagnosis of LUAD can be achieved with high sensitivity and specificity by using plasma as a substitute for BALF samples.
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Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Metilación de ADN , Detección Precoz del Cáncer , Proteínas de Homeodominio , Neoplasias Pulmonares , Regiones Promotoras Genéticas , Proteínas Supresoras de Tumor , Humanos , Masculino , Femenino , Persona de Mediana Edad , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/sangre , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/sangre , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/sangre , Detección Precoz del Cáncer/métodos , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Anciano , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/sangre , Líquido del Lavado Bronquioalveolar/química , Curva ROC , Adulto , Sensibilidad y Especificidad , Estudios de Casos y ControlesRESUMEN
BACKGROUND: The diagnosis of solitary pulmonary nodules has always been a difficult and important point in clinical research, especially granulomatous nodules (GNs) with lobulation and spiculation signs, which are easily misdiagnosed as malignant tumors. Therefore, in this study, we utilised a CT deep learning (DL) model to distinguish GNs with lobulation and spiculation signs from solid lung adenocarcinomas (LADCs), to improve the diagnostic accuracy of preoperative diagnosis. METHODS: 420 patients with pathologically confirmed GNs and LADCs from three medical institutions were retrospectively enrolled. The regions of interest in non-enhanced CT (NECT) and venous contrast-enhanced CT (VECT) were identified and labeled, and self-supervised labels were constructed. Cases from institution 1 were randomly divided into a training set (TS) and an internal validation set (IVS), and cases from institutions 2 and 3 were treated as an external validation set (EVS). Training and validation were performed using self-supervised transfer learning, and the results were compared with the radiologists' diagnoses. RESULTS: The DL model achieved good performance in distinguishing GNs and LADCs, with area under curve (AUC) values of 0.917, 0.876, and 0.896 in the IVS and 0.889, 0.879, and 0.881 in the EVS for NECT, VECT, and non-enhanced with venous contrast-enhanced CT (NEVECT) images, respectively. The AUCs of radiologists 1, 2, 3, and 4 were, respectively, 0.739, 0.783, 0.883, and 0.901 in the (IVS) and 0.760, 0.760, 0.841, and 0.844 in the EVS. CONCLUSIONS: A CT DL model showed great value for preoperative differentiation of GNs with lobulation and spiculation signs from solid LADCs, and its predictive performance was higher than that of radiologists.
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Adenocarcinoma del Pulmón , Aprendizaje Profundo , Neoplasias Pulmonares , Tomografía Computarizada por Rayos X , Humanos , Masculino , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/diagnóstico , Femenino , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico , Diagnóstico Diferencial , Anciano , Estudios Retrospectivos , Nódulo Pulmonar Solitario/diagnóstico por imagen , Nódulo Pulmonar Solitario/patología , Nódulo Pulmonar Solitario/diagnóstico , Adulto , Granuloma/diagnóstico por imagen , Granuloma/patología , Granuloma/diagnósticoRESUMEN
Objective: Lung adenocarcinoma poses a major global health challenge and is a leading cause of cancer-related deaths worldwide. This study is a review of three molecular biomarkers screened by machine learning that are not only important in the occurrence and progression of lung adenocarcinoma but also have the potential to serve as biomarkers for clinical diagnosis, prognosis evaluation and treatment guidance. Methods: Differentially expressed genes (DEGs) were identified using comprehensive GSE1987 and GSE18842 gene expression databases. A comprehensive bioinformatics analysis of these DEGs was conducted to explore enriched functions and pathways, relative expression levels, and interaction networks. Random Forest and LASSO regression analysis techniques were used to identify the three most significant target genes. The TCGA database and quantitative polymerase chain reaction (qPCR) experiments were used to verify the expression levels and receiver operating characteristic (ROC) curves of these three target genes. Furthermore, immune invasiveness, pan-cancer, and mRNA-miRNA interaction network analyses were performed. Results: Eighty-nine genes showed increased expression and 190 genes showed decreased expression. Notably, the upregulated DEGs were predominantly associated with organelle fission and nuclear division, whereas the downregulated DEGs were mainly associated with genitourinary system development and cell-substrate adhesion. The construction of the DEG protein-protein interaction network revealed 32 and 19 hub genes with the highest moderate values among the upregulated and downregulated genes, respectively. Using random forest and LASSO regression analyses, the hub genes were employed to identify three most significant target genes.TCGA database and qPCR experiments were used to verify the expression levels and ROC curves of these three target genes, and immunoinvasive analysis, pan-cancer analysis and mRNA-miRNA interaction network analysis were performed. Conclusion: Three target genes identified by machine learning: BUB1B, CENPF, and PLK1 play key roles in LUAD development of lung adenocarcinoma.