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BACKGROUND: Lactic acid (LA) can promote the malignant progression of tumors through the crosstalk with the tumor microenvironment (TME). However, the function of long non-coding RNAs (lncRNAs) related to LA metabolism in Wilms tumor (WT) remains unclear. METHODS: Gene expression data and clinical data of WT patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Through the ESTIMATE algorithm and Pearson correlation analysis, lncRNAs related to tumor immunity and LA metabolism were screened. Subsequently, Cox regression analysis and Lasso Cox regression analysis were used to construct a model. Furthermore, candidate genes were identified and a competitive endogenous RNA (ceRNA) network was conducted to explore the specific mechanism of characteristic genes. Finally, based on the strong clinical relevance of UNC5B-AS1, its expression and function were experimentally verified. RESULTS: The immune score and stromal score were found to be closely related to the prognosis of WT. Eventually, a prognostic model (TME-LA-LM) consisting of 6 lncRNAs was successfully identified. The model demonstrated favorable predictive ability and accuracy, with significant variation in immune infiltration and drug susceptibility observed between risk groups. Additionally, the study revealed the involvement of 2 candidate genes and 5 microRNAs (miRNAs) in the tumor's development. Notably, UNC5B-AS1 was highly expressed and found to promote the proliferation and migration of tumor cells. CONCLUSION: This study, for the first time, elucidated the prognostic signatures of WT using lncRNAs related to TME and LA metabolism. The fundings of this research offer valuable insights for future studies on immunotherapy, personalized chemotherapy and mechanism research.

Asunto(s)

Regulación Neoplásica de la Expresión Génica , Neoplasias Renales , Ácido Láctico , ARN Largo no Codificante , Microambiente Tumoral , Tumor de Wilms , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Humanos , Tumor de Wilms/genética , Tumor de Wilms/metabolismo , Tumor de Wilms/patología , Microambiente Tumoral/genética , Ácido Láctico/metabolismo , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/metabolismo , Pronóstico , MicroARNs/genética , MicroARNs/metabolismo , Femenino , Redes Reguladoras de Genes , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo

RESUMEN

BACKGROUND: Although progress has been made in accurate diagnosis and targeted treatments, breast cancer (BC) patients with metastasis still present a grim prognosis. With the continuous emergence and development of new personalized and precision medicine targeting specific tumor biomarkers, there is an urgent need to find new metastatic and prognostic biomarkers for BC patients. METHODS: We were dedicated to identifying genes linked to metastasis and prognosis in breast cancer through a combination of in silico analysis and experimental validation. RESULTS: A total of 25 overlap differentially expressed genes were identified. Ten hub genes (namely MRPL13, CTR9, TCEB1, RPLP0, TIMM8B, METTL1, GOLT1B, PLK2, PARL and MANBA) were identified and confirmed. MRPL13, TCEB1 and GOLT1B were shown to be associated with the worse overall survival (OS) and were optionally chosen for further verification by western blot. Only MRPL13 was found associated with cell invasion, and the expression of MRPL13 in metastatic BC was significantly higher than in primary BC. CONCLUSION: We proposed MRPL13 could be a potential novel biomarker for the metastasis and prognosis of breast cancer.

Asunto(s)

Biomarcadores de Tumor , Neoplasias de la Mama , Simulación por Computador , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , Regulación Neoplásica de la Expresión Génica , Metástasis de la Neoplasia , Perfilación de la Expresión Génica/métodos , Línea Celular Tumoral , Persona de Mediana Edad

RESUMEN

It has been discovered that Trichorhinophalangeal Syndrome-1 (TRPS1), a novel member of the GATA transcription factor family, participates in both normal physiological processes and the development of numerous diseases. Recently, TRPS1 has been identified as a new biomarker to aid in cancer diagnosis and is very common in breast cancer (BC), especially in triple-negative breast cancer (TNBC). In this review, we discussed the structure and function of TRPS1 in various normal cells, focused on its role in tumorigenesis and tumor development, and summarize the research status of TRPS1 in the occurrence and development of BC. We also analyzed the potential use of TRPS1 in guiding clinically personalized precision treatment and the development of targeted drugs.

Asunto(s)

Biomarcadores de Tumor , Neoplasias de la Mama , Proteínas de Unión al ADN , Proteínas Represoras , Factores de Transcripción , Humanos , Femenino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo , Regulación Neoplásica de la Expresión Génica , Carcinogénesis/genética , Carcinogénesis/metabolismo , Animales

RESUMEN

3,5,7-Trihydroxy-2-phenylchromen-4-one (THF) possesses a diverse range of pharmacological activities. Evidence suggests that THF exerts anticancer activity by distinct mechanisms of action. This study explores the anticancer potential of THF in human lung (A549) and skin (A431) cancer cells by employing different antiproliferative assays. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, neutral red uptake, sulphorhodamine B, and cell motility assays were used to confirm the anticancer potential of THF. Cell target-based and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays were used to explore the effect of THF on the initiation, promotion and progression phase biomarkers of carcinogenesis. THF suppresses the activity of lipoxygenase-5 up to ~40% in both A549 and A431 cells and up to ~50% hyaluronidase activity in A549 cells. qRT-PCR assay reveals that THF inhibits the activity of phosphatidyl inositol-3 kinase/protein kinase B/mammalian target of rapamycin in both cell lines, which is responsible for the initiation of cancer. It also arrests the G2/M phase of the cell cycle in A431 cells and increases the sub-diploid population in both A549 and A431 cell lines which leads to cell death. Annexin V-FITC assay confirmed that THF induces apoptosis and necrosis in A431 and A549 cell lines. Further investigation revealed that THF not only enhances reactive oxygen species production but also modulates mitochondrial membrane potential in both cell lines. It significantly inhibits S-180 tumour formation at 5 and 10 mg/kg bw, i.p. dose. An acute skin toxicity study on mice showed that erythema and edema scores are within the acceptable range, besides acceptable drug-likeness properties and non-toxic effects on human erythrocytes. Conclusively, THF showed potent anticancer activity on skin and lung carcinoma cell lines, suppressed the level of the biomarkers and inhibited tumour growth in mice.

Asunto(s)

Apoptosis , Neoplasias Pulmonares , Neoplasias Cutáneas , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Animales , Ratones , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/tratamiento farmacológico , Células A549 , Regulación hacia Abajo/efectos de los fármacos , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Antineoplásicos/farmacología

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To more accurately diagnose and treat patients with different subtypes of thyroid cancer, we constructed a diagnostic model related to the iodine metabolism of THCA subtypes. THCA expression profiles, corresponding clinicopathological information, and single-cell RNA-seq were downloaded from TCGA and GEO databases. Genes related to thyroid differentiation score were obtained by GSVA. Through logistic analyses, the diagnostic model was finally constructed. DCA curve, ROC curve, machine learning, and K-M analysis were used to verify the accuracy of the model. qRT-PCR was used to verify the expression of hub genes in vitro. There were 104 crossover genes between different TDS and THCA subtypes. Finally, 5 genes (ABAT, CHEK1, GPX3, NME5, and PRKCQ) that could independently predict the TDS subpopulation were obtained, and a diagnostic model was constructed. ROC, DCA, and RCS curves exhibited that the model has accurate prediction ability. K-M and subgroup analysis results showed that low model scores were strongly associated with poor PFI in THCA patients. The model score was significantly negatively correlated with T cell follicular helper. In addition, the diagnostic model was significantly negatively correlated with immune scores. Finally, the results of qRT-PCR corresponded with bioinformatics results. This diagnostic model has good diagnostic and prognostic value for THCA patients, and can be used as an independent prognostic indicator for THCA patients.

Asunto(s)

Yodo , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Biología Computacional/métodos , Femenino , Masculino , Aprendizaje Automático , Persona de Mediana Edad , Glándula Tiroides/patología , Glándula Tiroides/metabolismo , Curva ROC , Diferenciación Celular , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo

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Colorectal adenocarcinoma (COAD) has a poor prognosis. Cyclin-dependent kinase inhibitor 2A (CDKN2A) significantly affects the development and progression of various human tumors. However, the significance and pathological mechanisms of CDKN2A in COAD remain to be elucidated. We assessed expression levels, clinical significance, biological function, co-expressed genes, and enrichment of related pathways of CDKN2A in COAD using various databases, including The University of Alabama at Birmingham Cancer Data Analysis Portal, Gene Expression Profiling Interactive Analysis, Tumor Immune Estimation Resource, Human Protein Atlas, STRING, GeneMANIA, cBioPortal, and Linked Omics. Our investigation showed that CDKN2A was highly expressed in colon adenocarcinomas (P < .001). It is weakly expressed or not expressed in normal tissues. The survival time of patients with colon adenocarcinoma with high CDKN2A expression is significantly shorter than that of patients with low expression levels (P = .011). There was a significant positive correlation between the expression level of CDKN2A in colon adenocarcinoma tissues and the infiltration of CD4+ T cells, macrophages, and neutrophils. Moreover, there was a significant negative association between the expression level of CDKN2A in colon adenocarcinoma tissues and B cell infiltration. The ten hub genes included tumor protein 53, V-myc Avian Myelocytomatosis Viral Oncogene Homolog, AKT serine/threonine kinase 1, cyclin-dependent kinase 2, phosphatase and tensin homolog deleted on chromosome ten, cyclin D1, cyclin dependent kinase 4, cyclin dependent kinase inhibitor 1A, catenin beta 1, and B-Raf proto-oncogene, serine/threonine kinase. Mutations in the CDKN2A genome in colon adenocarcinoma reduce survival. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the differentially expressed genes were enriched in apoptotic signaling pathways and multiple pathways related to metabolic progression. Our results indicate that CDKN2A can be used as a marker of poor prognosis in patients with colon adenocarcinoma. CDKN2A may regulate the occurrence and development of colon adenocarcinomas by influencing immune cell infiltration and metabolic pathways.

Asunto(s)

Adenocarcinoma , Neoplasias del Colon , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Humanos , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Neoplasias del Colon/genética , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Regulación Neoplásica de la Expresión Génica , Proto-Oncogenes Mas , Perfilación de la Expresión Génica/métodos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico

RESUMEN

Pancreatic Cystic Neoplasms (PCN) represent a diverse group of tumors, some of which may progress to pancreatic cancer. Considering their high prevalence in the general population, the development of reliable biomarkers is crucial. The ideal biomarker will accurately diagnose the subtype of PCN and assess the risk of high-grade dysplasia or invasive cancer. Cyst fluid analysis has emerged as a promising approach to accomplish this goal, yet no single marker has yet gained unanimous support for routine inclusion in PCN evaluation.

Asunto(s)

Líquido Quístico , Quiste Pancreático , Neoplasias Pancreáticas , Humanos , Quiste Pancreático/diagnóstico , Líquido Quístico/química , Neoplasias Pancreáticas/diagnóstico , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo

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BACKGROUND: Prostate cancer (PCa) remains a significant global health issue, exhibiting a spectrum of clinical behaviours from indolent to aggressive. Biomarkers are crucial for risk assessment, treatment selection and prognosis prediction. Despite their importance, accurately evaluating PCa aggressiveness and guiding personalised treatment strategies present challenges. This review aims to evaluate biomarkers for assessing recurrence risk following radical prostatectomy, with a focus on personalised follow-up and timely intervention for high-risk patients. This review assesses the clinical significance of immunohistochemical biomarkers, including LIM domain kinase 1 (LIMK1), Antigen Kiel 67 (Ki67), PTEN and ERG, in PCa management. A comprehensive literature review examined the correlation between these biomarkers and biochemical recurrence (BCR) in patients undergoing radical prostatectomy. Our search included articles published between 2019 and 2024, yielding 87 articles, with 7 focused on the correlation between LIMK1 and BCR, 46 on Ki67 and 34 on PTEN/ERG biomarkers. After applying the exclusion criteria, 36 articles were included for review. LIMK1, a serine/threonine kinase, is highly expressed in cancers like PCa. It influences cell survival and motility through actin cytoskeleton reorganisation, correlating with poor prognosis, aggressive tumour behaviour and BCR. Similarly, Ki67, a marker of cell proliferation, predicts high-risk PCa and worse prognosis, particularly in castration-resistant cases, although its association with recurrence risk remains debated. PTEN loss and ERG fusion are prevalent genetic alterations in PCa, with PTEN loss linked to poor prognosis and ERG fusion associated with increased disease progression and BCR post-prostatectomy. Integrating these biomarkers into clinical practice can enhance risk stratification and inform personalised treatment strategies for patients with PCa. Despite promising findings, further validation studies and standardisation of detection methods are needed to ensure the clinical utility of these biomarkers. Continued research is essential to validate and optimise the clinical utility of these biomarkers, paving the way for more effective PCa management strategies and improved patient outcomes and quality of life.

Asunto(s)

Biomarcadores de Tumor , Inmunohistoquímica , Recurrencia Local de Neoplasia , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Medición de Riesgo , Valor Predictivo de las Pruebas

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This Corrigendum relates to the following article: https://doi.org/10.2340/actadv.v104.13381.

Asunto(s)

Carcinoma de Células Escamosas , Queratoacantoma , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/metabolismo , Queratoacantoma/patología , Queratoacantoma/metabolismo , Queratoacantoma/inmunología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/metabolismo , Masculino , Femenino , Anciano , Proteínas de Punto de Control Inmunitario/metabolismo , Persona de Mediana Edad , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Inmunohistoquímica , Anciano de 80 o más Años

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Pancreatic cancer (PC) is a challenging and heterogeneous disease with a high mortality rate. Despite advancements in treatment, the prognosis for PC patients remains poor, with a high chance of disease recurrence. Biomarkers are crucial for diagnosing cancer, predicting patient prognosis and selecting treatments. However, the current lack of effective biomarkers for PC could contribute to the insufficiency of existing treatments. These findings underscore the urgent need to develop novel strategies to fight this disease. This study utilized multiple comprehensive bioinformatic analyses to identify potential therapeutic target genes in PC, focusing on histone lysine demethylases (KDMs). We found that high expression levels of KDM family genes, particularly KDM1A, KDM5A and KDM5B, were associated with improved overall survival in the cohort. Furthermore, the infiltration of various immune cells, including B cells, neutrophils, CD8+ T cells, dendritic cells, and macrophages, was positively correlated with KDM1A, KDM5A, and KDM5B expression. Moreover, MetaCore pathway analysis revealed interesting connections between KDM1A and the cell cycle and proliferation, between KDM5A and DNA damage and double-strand break repair through homologous recombination, and between KDM5B and WNT/ß-catenin signaling. These findings suggest that KDM1A, KDM5A and KDM5B may serve as promising biomarkers and therapeutic targets for PC, a disease of high importance due to its aggressive nature and urgent need for novel biomarkers to improve diagnosis and treatment.

Asunto(s)

Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , Histona Demetilasas con Dominio de Jumonji , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Histona Demetilasas con Dominio de Jumonji/metabolismo , Histona Demetilasas con Dominio de Jumonji/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , Biología Computacional , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Histona Demetilasas/metabolismo , Histona Demetilasas/genética , Terapia Molecular Dirigida/métodos , Proteína 2 de Unión a Retinoblastoma/metabolismo , Proteína 2 de Unión a Retinoblastoma/genética , Vía de Señalización Wnt/genética , Proliferación Celular/genética , Proteínas Nucleares , Proteínas Represoras

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The tetraspanin family of membrane proteins is essential for controlling different biological processes such as cell migration, penetration, adhesion, growth, apoptosis, angiogenesis and metastasis. The present review summarized the current knowledge regarding the expression and roles of tetraspanins in different types of cancer of the digestive system, including gastric, liver, colorectal, pancreatic, esophageal and oral cancer. Depending on the type and context of cancer, tetraspanins can act as either tumor promoters or suppressors. In the present review, the importance of tetraspanins in serving as biomarkers and targets for different types of digestive system­related cancer was emphasized. Additionally, the molecular mechanisms underlying the involvement of tetraspanins in cancer progression and metastasis were explored. Furthermore, the current challenges are addressed and future research directions for advancing investigations related to tetraspanins in the context of digestive system malignancies are proposed.

Asunto(s)

Neoplasias del Sistema Digestivo , Tetraspaninas , Humanos , Tetraspaninas/metabolismo , Tetraspaninas/genética , Neoplasias del Sistema Digestivo/metabolismo , Neoplasias del Sistema Digestivo/genética , Neoplasias del Sistema Digestivo/patología , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Animales

RESUMEN

Cancer-associated fibroblasts (CAFs) are a diverse stromal cell population within the tumour microenvironment, where they play fundamental roles in cancer progression and patient prognosis. Multiple lines of evidence have identified that CAFs are critically involved in shaping the structure and function of the tumour microenvironment with numerous functions in regulating tumour behaviours, such as metastasis, invasion, and epithelial-mesenchymal transition (EMT). CAFs can interact extensively with cancer cells by producing extracellular vesicles (EVs), multiple secreted factors, and metabolites. Notably, CAF-derived EVs have been identified as critical mediators of cancer therapy resistance, and constitute novel therapy targets and biomarkers in cancer management. This review aimed to summarize the biological roles and detailed molecular mechanisms of CAF-derived EVs in mediating cancer resistance to chemotherapy, targeted therapy agents, radiotherapy, and immunotherapy. We also discussed the therapeutic potential of CAF-derived EVs as novel targets and clinical biomarkers in cancer clinical management, thereby providing a novel therapeutic strategy for enhancing cancer therapy efficacy and improving patient prognosis.

Asunto(s)

Fibroblastos Asociados al Cáncer , Resistencia a Antineoplásicos , Vesículas Extracelulares , Neoplasias , Microambiente Tumoral , Humanos , Vesículas Extracelulares/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/terapia , Biomarcadores de Tumor/metabolismo , Animales , Transición Epitelial-Mesenquimal , Relevancia Clínica

RESUMEN

INTRODUCTION: Mutated human epidermal growth factor receptor 2 (HER2) is an oncogene with critical pathogenic roles in breast cancer. HER2-low-positive breast cancer is a recently described subtype. We aimed to explore the clinical and molecular characteristics of gastric cancer with low HER2 expression, drawing on recent developments in breast cancer subtypes. MATERIALS AND METHODS: This retrospective study involved 129 patients with HER2-non-amplified gastric cancer treated in Iwate prefectural Iwai Hospital from 2013 to 2019. Tumors were classified as HER2-null or low-positive based on immunohistochemistry score 0 or 1 + or 2 + with HER2 negativity in situ hybridization, respectively. Statistical analyses, including Kaplan-Meier analyses and Cox proportional hazards model were conducted. RESULTS: Low HER2 expression was present in 26% (33/129) of the patients. Clinicopathological characteristics were not significantly different between the HER2-low and null groups. Kaplan-Meier analysis of overall survival was significantly longer in the HER2-low group than in the HER2-null group (P = 0.01). In multivariate Cox regression analysis, HER2-null status was associated with worse survival (hazard ratio 3.01; 95% confidence interval 1.18-7.65; and P = 0.02). CONCLUSION: This study highlights the prognostic importance of low HER2 expression in gastric cancer, similar to that observed in HER2-low-positive breast cancer, and suggests reclassification of gastric cancer to improve personalized treatment. Future studies should elucidate the molecular underpinnings of low HER2 expression in gastric cancer to guide novel therapeutic strategies and improve outcomes.

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Receptor ErbB-2 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Femenino , Estudios Retrospectivos , Pronóstico , Anciano , Persona de Mediana Edad , Masculino , Estimación de Kaplan-Meier , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Adulto , Anciano de 80 o más Años , Inmunohistoquímica , Modelos de Riesgos Proporcionales

RESUMEN

BACKGROUND: Desmoglein-2 (DSG2) has been reported to play pivotal roles in various diseases. However, its roles in cervical cancer (CC) remain insufficiently elucidated. Here, we aimed to comprehensively explore the functional mechanisms of DSG2 in CC using bioinformatics and experimental methods. METHODS: Several online databases, including Gene Expression Profiling Interactive Analysis (GEPIA), ONCOMINE, LinkedOmics, MetaScape, Human protein atlas (HPA), OMICS and single-cell RNA sequencing (scRNA-seq) data were used to explore the expression, prognosis, gene mutations, and potential signaling pathway of DSG2 in CC. Quantitative real-time PCR (qRT-PCR) and western blotting were used to measure DSG2 expression in collected samples. Experimental assays were conducted to verify the effects of dysregulated DSG2 on cervical cell lines in vitro. RESULTS: Bioinformatic analyses revealed that DSG2 was significantly up-regulated in CC compared to normal cervical tissues at both mRNA and protein levels. Elevated DSG2 levels were also associated with poor prognosis and clinical parameters (e.g., cancer stages, tumor grade, nodal metastasis status, etc.). DSG2 expression was predominantly observed in epithelial cells, increasing with disease progression on a single-cell resolution. Additionally, up-regulation of DSG2 significantly enhanced tumor purity by reducing the infiltration of immune cells (e.g., B cells, T cells, NK cells, etc.). Over-expression of DSG2 was further validated in collected CC samples at both mRNA and protein levels. Knockdown of DSG2 markedly reduced the proliferation and invasion of CC cell lines in vitro. CONCLUSIONS: In summary, elevated levels of DSG2 were significantly associated with poor prognosis and diminished immune infiltration in CC. Thus, DSG2 may serve as a potential therapeutic and diagnostic biomarker for CC.

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Desmogleína 2 , Regulación Neoplásica de la Expresión Génica , Regulación hacia Arriba , Neoplasias del Cuello Uterino , Desmogleína 2/genética , Desmogleína 2/metabolismo , Humanos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/inmunología , Femenino , Proliferación Celular , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral

RESUMEN

Purpose: We assessed whether NICD1 expression, c-MYC expression, and P63 expression by immunohistochemistry (IHC) correlate with prognosis and high-risk clinicopathological features in lacrimal gland adenoid cystic carcinoma (ACC). Methods: Records of patients with lacrimal gland ACC who underwent surgery between 1998 to 2018 were reviewed. Clinicopathologic and treatment data were collected. Tumor tissues were subjected to light microscopy and IHC. Results: Of 43 patients treated during the study period, 21 had archived tumor tissue available and were included. The median age at diagnosis was 47 years, and 13 patients (62%) were male. Thirteen patients (62%) had T2 disease, and none had nodal or distant metastasis at diagnosis. Tumors were positive for NICD1 expression in eight cases (38%), c-MYC expression in eight (38%), and P63 expression in 11 (52%). Positive NICD1 expression was associated with predominantly solid (vs. cribriform/tubular) pattern (P < 0.001), treatment with orbital exenteration (vs. eye-sparing surgery) (P = 0.008), local recurrence (P = 0.047), and death (P = 0.012). Negative P63 expression was associated with predominantly solid pattern (P = 0.001), local recurrence (P = 0.012), distant metastasis (P = 0.001), and death (P = 0.035). A higher percentage of tumor cells staining for c-MYC was associated with presence of perineural invasion (P = 0.036). Positive NICD1 expression was associated with worse disease-free survival (hazard ratio, 6.27; 95% CI, 1.29-30.46), whereas positive P63 expression was associated with better disease-free survival (hazard ratio, 0.03; 95% CI, 0.0002-0.26). Conclusions: IHC for NICD1 and P63 should be considered in lacrimal gland ACC because of their prognostic value and potential as treatment targets.

Asunto(s)

Biomarcadores de Tumor , Carcinoma Adenoide Quístico , Neoplasias del Ojo , Enfermedades del Aparato Lagrimal , Proteínas Proto-Oncogénicas c-myc , Receptor Notch1 , Humanos , Carcinoma Adenoide Quístico/metabolismo , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/diagnóstico , Masculino , Persona de Mediana Edad , Femenino , Adulto , Pronóstico , Enfermedades del Aparato Lagrimal/metabolismo , Enfermedades del Aparato Lagrimal/patología , Enfermedades del Aparato Lagrimal/diagnóstico , Anciano , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Neoplasias del Ojo/metabolismo , Neoplasias del Ojo/patología , Neoplasias del Ojo/diagnóstico , Estudios Retrospectivos , Biomarcadores de Tumor/metabolismo , Receptor Notch1/metabolismo , Inmunohistoquímica , Adulto Joven , Proteínas de la Membrana , Factores de Transcripción , Proteínas Supresoras de Tumor

RESUMEN

BACKGROUND: Despite the favorable therapeutic efficacy observed with ICI monotherapy, the majority of non-small cell lung cancer (NSCLC) patients do not respond. Therefore, identifying patients who could optimally benefit from ICI treatment remains a challenge. METHODS: Among 183 patients with advanced or recurrent NSCLC who received ICI monotherapy, we analyzed 110 patients whose pre- and post-treatment plasma samples were available. Seventy-three soluble immune mediators were measured at ICI initiation and 6 weeks later. To identify useful biomarkers, we analyzed the association of pre-treatment levels and on-treatment changes of soluble immune mediators with survival of patients. The associations of pre-treatment or on-treatment biomarkers with irAE development, PD-L1 expression, CD8+ TIL density, and neutrophil to lymphocyte ratio (NLR) were also analyzed. RESULTS: Univariate analysis showed that pre-treatment biomarkers included 6 immune mediators, whereas on-treatment biomarkers included 8 immune mediators. Multivariate analysis showed that pre-treatment biomarkers included 4 immune mediators (CCL19, CCL21, CXCL5, CXCL10), whereas on-treatment biomarkers included 5 immune mediators (CCL7, CCL19, CCL23, CCL25, IL-32). IrAE development was associated with on-treatment change in CCL23. PD-L1 expression was associated with the pre-treatment levels of TNFSF13B and the on-treatment change in CCL25. CD8+ TIL density was associated with the pre-treatment CXCL10 level, whereas NLR was correlated with pre-treatment levels of CCL13 and CCL17. CONCLUSION: We identified several soluble immune mediators as pre-treatment and on-treatment biomarkers of survival in patients with NSCLC treated with ICI monotherapy. Some of these biomarkers were associated with other possible predictors, including irAE development, PD-L1 expression, CD8+ TIL density and NLR. Further large-scale studies are needed to establish biomarkers for patients with NSCLC who received ICI monotherapy.

Asunto(s)

Antígeno B7-H1 , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Microambiente Tumoral , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Microambiente Tumoral/inmunología , Masculino , Femenino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Anciano , Biomarcadores de Tumor/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Adulto , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Anciano de 80 o más Años , Pronóstico , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo

RESUMEN

BACKGROUND: To assess the distribution characteristics of immune infiltration and lymphovascular invasion in breast cancer skin recurrence patients. METHODS: We retrospectively analyzed the clinicopathological data of patients who underwent radical surgery for primary breast cancer and experienced skin recurrence between January 2001 and April 2019. Immune and lymphovascular biomarkers were quantified in primary breast cancers, skin lesions and visceral metastatic lesions. Differences in biomarkers distribution between matched tissues were statistically analyzed using the Wilcoxon signed-rank test and Kruskal-Wallis one-way ANOVA. RESULTS: A total of 71 female breast cancer patients were reviewed in this study. Our study found that the expression levels of various lymphocyte immune markers in primary tumor specimens were higher than those in skin recurrences. The expression of CD8, CD57 and CD31 in primary breast cancer was higher than those in the skin. Compared to visceral metastatic lesions, D2-40 was highly expressed in the skin, while CD8 tended to decrease. In the skin specimens, the expression of CD8 (P < 0.001), FOXP3 (P = 0.006) and CD68 (P < 0.001) in the intratumoral area was higher, while the expression of CD57 (P < 0.001) was higher in the peritumoral area. Analyzing specimens from the same patient at different time points of skin progression, it was found that the expression of peritumoral CD4 decreased (P = 0.044) as the disease progressed. The low expression of D2-40 and CD163 in the skin lesions suggested a decrease in DFS. CONCLUSION: The immune microenvironment of breast cancer skin recurrence may be in a state of suppression, and this suppression may intensify with disease progression. The pattern of skin recurrence may be more inclined toward lymphatic invasion. Our study provides new insights into the biological behaviors of this disease and its response to immunotherapy.

Asunto(s)

Neoplasias de la Mama , Linfocitos Infiltrantes de Tumor , Recurrencia Local de Neoplasia , Neoplasias Cutáneas , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Persona de Mediana Edad , Estudios Retrospectivos , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/metabolismo , Anciano , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Adulto , Metástasis Linfática/patología , Metástasis Linfática/inmunología , Biomarcadores de Tumor/metabolismo , Microambiente Tumoral/inmunología , Invasividad Neoplásica , Pronóstico

RESUMEN

BACKGROUND: SEPT9 is a pivotal cytoskeletal GTPase that regulates diverse biological processes encompassing mitosis and cytokinesis. While previous studies have implicated SEPT9 in tumorigenesis and development; comprehensive pan-cancer analyses have not been performed. This study aims to systematically explore its role in cancer screening, prognosis, and treatment, addressing this critical gap. METHODS: Gene and protein expression data containing clinical information were obtained from public databases for pan-cancer analyses. Additionally, clinical samples from 90 patients with lung squamous cell carcinoma (LUSC) were used to further experimentally validate the clinical significance of SEPT9. In addition, the molecular docking tool was used to analyze the affinities between SEPT9 protein and drugs. RESULTS: SEPT9 is highly expressed in various cancers, and its aberrant expression correlates with genetic alternations and epigenetic modifications, leading to adverse clinical outcomes. Take LUSC as an example, additional dataset analyses and immunohistochemical experiments further confirm the diagnostic and prognostic values as well as the clinical relevance of the SEPT9 gene and protein. Functional enrichment, single-cell expression, and immune infiltration analyses revealed that SEPT9 promotes malignant tumor progression and modulates the immune microenvironments, enabling patients to benefit from immunotherapy. Moreover, drug sensitivity and molecular docking analyses showed that SEPT9 is associated with the sensitivity and resistance of multiple drugs and has stable binding activity with them, including Vorinostat and OTS-964. To harness its prognostic and therapeutic potential in LUSC, a mitotic spindle-associated prognostic model including SEPT9, HSF1, ARAP3, KIF20B, FAM83D, TUBB8, and several clinical characteristics, was developed. This model not only improves clinical outcome predictions but also reshapes the immune microenvironment, making immunotherapy more effective for LUSC patients. CONCLUSION: This is the first study to systematically analyze the role of SEPT9 in cancers and innovatively apply the mitotic spindle-associated model to LUSC, fully demonstrating its potential as a valuable biomarker for cancer screening and prognosis, and highlighting its application value in promoting immunotherapy and chemotherapy, particularly for LUSC.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias Pulmonares , Simulación del Acoplamiento Molecular , Septinas , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Septinas/genética , Septinas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Pronóstico , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral/inmunología , Masculino , Femenino

RESUMEN

Head and neck squamous cell carcinomas (HNSCCs), a heterogeneous group of cancers that arise from the mucosal epithelia cells in the head and neck areas, present great challenges in diagnosis, treatment and prognosis due to their complex aetiology and various clinical manifestations. Several factors, including smoking, alcohol consumption, oncogenic genes, growth factors, Epstein­Barr virus and human papillomavirus infections can contribute to HNSCC development. The unpredictable tumour microenvironment adds to the complexity of managing HNSCC. Despite significant advances in therapies, the prediction of outcome after treatment for patients with HNSCC remains poor, and the 5­year overall survival rate is low due to late diagnosis. Early detection greatly increases the chances of successful treatment. The present review aimed to bring together the latest findings related to the molecular mechanisms of HNSCC carcinogenesis and progression. Comprehensive genomic, transcriptomic, metabolomic, microbiome and proteomic analyses allow researchers to identify important biological markers such as genetic alterations, gene expression signatures and protein markers that drive HNSCC tumours. These biomarkers associated with the stages of initiation, progression and metastasis of cancer are useful in the management of patients with cancer in order to improve their life expectancy and quality of life.

Asunto(s)

Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/virología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Microambiente Tumoral , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinogénesis/genética , Pronóstico , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/patología

RESUMEN

The translation of discoveries on extracellular vesicle (EV) based cancer biomarkers to personalised precision oncology requires the development of robust, sensitive and specific assays that are amenable to adoption in the clinical laboratory. Whilst a variety of elegant approaches for EV liquid biopsy have been developed, most of them remain as research prototypes due to the requirement of a high level of microfabrication and/or sophisticated instruments. Hence, this study is set to develop a simple DNA aptamer-enabled and fluorescence polarisation-based homogenous assay that eliminates the need to separate unbound detection ligands from the bound species for EV detection. High specificity is achieved by immobilising EVs with one set of antibodies and subsequently detecting them with a DNA aptamer targeting a distinct EV biomarker. This two-pronged strategy ensures the removal of most, if not all, non-EV substances in the input biofluids, including soluble proteins, protein aggregates or non-vesicular particles, prior to quantifying biomarker-positive EVs. A limit of detection of 5.0 × 106 EVs/mL was achieved with a linear quantification range of 5.0 × 108 to 2.0 × 1010 EVs/mL. Facilitated by a multiple parametric analysis strategy, this aptamer-guided fluorescence polarisation assay was capable of distinguishing EVs from three different types of solid cancer cells based on quantitative differences in the levels of the same sets of biomarkers on EVs. Given the simplicity of the method and its ease of implementation in automated clinical biochemistry analysers, this assay could be exploited for future EV-based continuous and real-time monitoring of the emergence of new macro- or micro-metastasis, cancer progression as well as the response to treatment throughout different stages of cancer management in the clinic.

Asunto(s)

Aptámeros de Nucleótidos , Biomarcadores de Tumor , Vesículas Extracelulares , Humanos , Vesículas Extracelulares/metabolismo , Biopsia Líquida/métodos , Aptámeros de Nucleótidos/metabolismo , Biomarcadores de Tumor/metabolismo , Polarización de Fluorescencia/métodos , Línea Celular Tumoral , Neoplasias/metabolismo