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Introduction: blood centres are often faced with the problem of donor lapsing resulting in loss of donors from the already strained donor pool. In Zimbabwe, 70% of the donated blood comes from younger donors aged 40 years and below, who at the same time, have high attrition rates. This study seeks to apply the concept of survival analysis in analysing blood donor lapsing rates. Methods: in analysing the donor lapsing and retention rates, data on 450 first-time blood donors at the National Blood Service Zimbabwe, in Harare´s blood bank for the period 2014 to 2017 was extracted from the donors´ database. The Cox proportional hazards (Cox PH) and Kaplan-Meier methods were applied in the analysis. Donor demographic characteristics suspected of having effect on donor lapsing and retention were identified and analysed. Results: the study findings show that 56.9% of the donors had lapsed by the end of the four-year study period. Results from the multiple Cox PH model indicate that donor age had a significant effect on blood donor retention time (p = 0.000918 < 0.05). The hazard ratio (HR) = 0.615 with 95% CI: (0.461; 0.820) shows that the relatively older donors had a lower hazard (38.5% lower) of lapsing compared to the hazard for younger donors. The effect of gender, blood donor group and donation time interval on donor retention and attrition were not statistically significant. Male donors had HR = 1.03; 95% CI (0.537; 1.99) with (p = 0.922 > 0.05) and donors with a 4-month interval between donations had HR = 1.31; 95% CI (0.667; 2.59) with (p = 0.430 > 0.05). Conclusion: the study confirmed the problem of donor attrition faced by blood centres. The age of the donor had a significant effect on the retention time of blood donors before lapsing. The older the blood donor, the lower the risk of lapsing. The Zimbabwe National Blood Service (NBSZ) Blood Centre authorities should have a critical mass of individuals above 40 years as potential blood donors because of their reliability in blood donation according to the study findings.
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Bancos de Sangre , Donantes de Sangre , Humanos , Zimbabwe , Donantes de Sangre/estadística & datos numéricos , Masculino , Femenino , Adulto , Adulto Joven , Persona de Mediana Edad , Bancos de Sangre/estadística & datos numéricos , Factores de Edad , Factores de Tiempo , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Estimación de Kaplan-Meier , AdolescenteRESUMEN
Background: Acute myocardial infarction (AMI) is a critical cardiovascular disease with high morbidity and mortality. Identifying practical parameters for predicting long-term mortality is crucial in this patient group. The percentage of mean arterial pressure (%MAP) is a useful parameter used to assess peripheral artery disease. It can be easily calculated from ankle pulse volume recording. Previous studies have shown that %MAP is a useful predictor of all-cause mortality in specific populations, but its relationship with mortality in AMI patients is unclear. Methods: In this observational cohort study, 191 AMI patients were enrolled between November 2003 and September 2004. Ankle-brachial index (ABI) and %MAP were measured using an ABI-form device. All-cause and cardiovascular mortality data were collected from a national registry until December 2018. Cox proportional hazards model and Kaplan-Meier survival plot were used to analyze the association between %MAP and long-term mortality in AMI patients. Results: The median follow-up to mortality was 65 months. There were 130 overall and 36 cardiovascular deaths. High %MAP was associated with increased overall mortality after multivariable analysis (HR = 1.062; 95% CI: 1.017-1.109; p =0.006). However, high % MAP was only associated with cardiovascular mortality in the univariable analysis but became insignificant after the multivariable analysis. Conclusions: In conclusion, this study is the first to evaluate the usefulness of %MAP in predicting long-term mortality in AMI patients. Our study shows that %MAP might be an independent predictor of long-term overall mortality in AMI patients and has better predictive power than ABI.
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Índice Tobillo Braquial , Presión Arterial , Infarto del Miocardio , Humanos , Infarto del Miocardio/mortalidad , Infarto del Miocardio/fisiopatología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estimación de Kaplan-Meier , Enfermedad Arterial Periférica/mortalidad , Enfermedad Arterial Periférica/fisiopatología , Factores de Riesgo , Pronóstico , Modelos de Riesgos Proporcionales , Estudios de CohortesRESUMEN
INTRODUCTION: Visceral metastasis is an important predictor for poor outcomes in prostate cancer, however, the prognostic significance surrounding the specific sites of visceral metastasis remains unclear. The aim of this study was to evaluate the impact of different visceral metastatic sites on survival in patients with prostate cancer. METHODS: We identified patients with metastatic prostate cancer between January 1, 2010 and December 31, 2023 using the TriNetX database. Patients were divided into 4 cohorts according to their specific metastatic sites: lung metastases, brain metastases, liver metastases, and bone metastases. Survival analysis was calculated using the Kaplan-Meier method and Cox regression models. RESULTS: In total, 59,875 patients diagnosed with metastatic prostate cancer were identified, with 39,495 (65.2%) having bone metastases, 7,573 (12.5%) lung metastases, 5,240 (8.7%) brain metastases, and 7,567 (12.5%) liver metastases. The median overall survival was 44.4 months for patients with bone metastases, 31.9 months for lung metastases, 9.6 months for brain metastases, and 10 months for liver metastases. Lung metastases were associated with an improved survival when compared with liver and brain metastases. For patients with two visceral metastatic sites or concomitant bone metastases, liver metastases were related to worse outcomes. Asian patients experienced better OS than Caucasian and African American patients in visceral metastatic prostate cancer. CONCLUSION: Patients with lung metastases experienced better survival outcomes in prostate cancer with only one visceral metastatic site. Liver metastases were associated with worse outcomes when there were two visceral metastatic sites combined or concomitant bone metastases. Asian patients displayed improved survival rates when compared with both Caucasian and African American patients in visceral metastatic prostate cancer.
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Neoplasias Óseas , Neoplasias Hepáticas , Neoplasias Pulmonares , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/mortalidad , Anciano , Neoplasias Óseas/secundario , Neoplasias Óseas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/mortalidad , Persona de Mediana Edad , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Pronóstico , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/mortalidad , Estimación de Kaplan-Meier , Metástasis de la Neoplasia , Anciano de 80 o más Años , Modelos de Riesgos ProporcionalesRESUMEN
INTRODUCTION: Heart transplantation is the gold standard for advanced heart failure treatment. This study examines the survival rates and risk factors for early mortality in adult heart transplant recipients at a Brazilian center. METHODS: This retrospective cohort study involved 255 adult heart transplant patients from a single center in Brazil. Data were collected from medical records and databases including three defined periods (2012-2015, 2016-2019, and 2020-2022). Statistical analysis employed Kaplan-Meier survival curves, Cox proportional hazards analysis for 30-day mortality risk factors, and Log-rank tests. RESULTS: The recipients were mostly male (74.9%), and the mean age was 46.6 years. Main causes of heart failure were idiopathic dilated cardiomyopathy (33.9%), Chagas cardiomyopathy (18%), and ischemic cardiomyopathy (14.3%). The study revealed an overall survival of 68.1% at one year, 58% at five years, and 40.8% at 10 years after heart transplantation. Survivalimproved significantly over time, combining the most recent periods (2016 to 2022) it was 73.2% in the first year and 63% in five years. The main risk factors for 30-day mortality were longer time on cardiopulmonary bypass, the initial period of transplants (2012 to 2015), older age of the donor, and nutritional status of the donor (overweight or obese). The main causes of death within 30 days post-transplant were infection and primary graft dysfunction. CONCLUSION: The survival analysis by period demonstrated that the increased surgical volume, coupled with the team's experience and modifications to the immunosuppression protocol, contributed to the improved early and mid-term outcomes.
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Insuficiencia Cardíaca , Trasplante de Corazón , Humanos , Masculino , Trasplante de Corazón/mortalidad , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Brasil/epidemiología , Adulto , Factores de Riesgo , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/cirugía , Estimación de Kaplan-Meier , Tasa de Supervivencia , Análisis de Supervivencia , Factores de Tiempo , Modelos de Riesgos ProporcionalesRESUMEN
Recent reports have shown that pre-treatment low muscle mass may lead to poorer outcomes for cancer patients. We explored the correlation between Visceral Adipose Tissue (VAT), Subcutaneous Adipose Tissue (SAT), and Muscle Mass (MM) as measured by CT scans, and overall survival (OS) following diagnosis of colorectal cancer (CRC). We conducted a retrospective review of medical records and CT scans of patients diagnosed with CRC between 2007 and 2018. Demographics, pathology, and clinical parameters were collected. Using Image-J software, we measured VAT, SAT, and MM. Survival rates were analyzed using Kaplan-Meier curves, and prognostic factors were assessed using multivariate Cox regression. Analysis included 408 patients with a mean age of 56.9 years and a median follow-up of 93.3 months. Colon and rectum/rectosigmoid colon cancers were equally distributed. The 5-year OS rate was 67.8%. There was no significant difference in OS rates based on SAT or VAT. However, higher MM was associated with a improved 5-year OS rate. Factors such as age, stage, grade, and surgery were also associated to OS rates. These findings suggest that higher muscle mass may lead to better outcomes for CRC patients, highlighting the potential impact of exercise and nutritional interventions on patient outcomes.
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Neoplasias Colorrectales , Humanos , Masculino , Persona de Mediana Edad , Femenino , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Estudios Retrospectivos , Anciano , Pronóstico , Grasa Intraabdominal/patología , Adulto , Centros de Atención Terciaria , Tomografía Computarizada por Rayos X , Tasa de Supervivencia , Grasa Subcutánea/patología , Grasa Subcutánea/diagnóstico por imagen , Estimación de Kaplan-Meier , Músculo Esquelético/patología , Músculo Esquelético/diagnóstico por imagenRESUMEN
BACKGROUND AND AIMS: Preoperative prediction of axillary lymph node (ALN) burden in patients with early-stage breast cancer is pivotal for individualised treatment. This study aimed to develop a MRI radiomics model for evaluating the ALN burden in early-stage breast cancer and to provide biological interpretability to predictions by integrating radiogenomic data. METHODS: This study retrospectively analyzed 1211 patients with early-stage breast cancer from four centers, supplemented by data from The Cancer Imaging Archive (TCIA) and Duke University (DUKE). MRI radiomic features were extracted from dynamic contrast-enhanced MRI images and an ALN burden-related radscore was constructed by the backpropagation neural network algorithm. Clinical and combined models were developed, integrating ALN-related clinical variables and radscore. The Kaplan-Meier curve and log-rank test were used to assess the prognostic differences between the predicted high- and low-ALN burden groups in both Center I and DUKE cohorts. Gene set enrichment and immune infiltration analyses based on transcriptomic TCIA and TCIA Breast Cancer dataset were used to investigate the biological significance of the ALN-related radscore. RESULTS: The MRI radiomics model demonstrated an area under the curve of 0.781-0.809 in three validation cohorts. The predicted high-risk population demonstrated a poorer prognosis (log-rank P < .05 in both cohorts). Radiogenomic analysis revealed migration pathway upregulation and cell differentiation pathway downregulation in the high radscore groups. Immune infiltration analysis confirmed the ability of radiological features to reflect the heterogeneity of the tumor microenvironment. CONCLUSIONS: The MRI radiomics model effectively predicted the ALN burden and prognosis of early-stage breast cancer. Moreover, radiogenomic analysis revealed key cellular and immune patterns associated with the radscore.
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Axila , Neoplasias de la Mama , Ganglios Linfáticos , Imagen por Resonancia Magnética , Estadificación de Neoplasias , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Femenino , Imagen por Resonancia Magnética/métodos , Ganglios Linfáticos/patología , Ganglios Linfáticos/diagnóstico por imagen , Persona de Mediana Edad , Axila/diagnóstico por imagen , Axila/patología , Pronóstico , Adulto , Estimación de Kaplan-Meier , Metástasis Linfática/diagnóstico por imagen , Anciano , Estudios Retrospectivos , RadiómicaRESUMEN
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 ProporcionalesRESUMEN
BACKGROUND: The addition of trabectedin to doxorubicin, followed by trabectedin maintenance, may have superior efficacy to doxorubicin alone as first-line treatment in patients with advanced leiomyosarcoma. METHODS: We conducted a phase 3 trial involving patients with metastatic or unresectable leiomyosarcoma who had not received chemotherapy previously. Patients were randomly assigned to receive either single-agent doxorubicin (six cycles) or doxorubicin plus trabectedin (six cycles), with continued trabectedin as maintenance therapy in patients in the doxorubicin-trabectedin group who did not have disease progression. Surgery to resect residual disease was allowed in each group after six cycles of therapy. Analyses of progression-free survival (primary end point) and overall survival (secondary end point) were adjusted for two stratification factors: tumor origin site (uterine vs. soft tissue) and disease stage (locally advanced vs. metastatic). The primary end-point results were reported previously. RESULTS: A total of 150 patients underwent randomization. At a median follow-up of 55 months (interquartile range, 49 to 63), a total of 107 patients had died (47 in the doxorubicin-trabectedin group and 60 in the doxorubicin group). The median overall survival was longer in the doxorubicin-trabectedin group (33 months; 95% confidence interval [CI], 26 to 48) than in the doxorubicin group (24 months; 95% CI, 19 to 31); the adjusted hazard ratio for death was 0.65 (95% CI, 0.44 to 0.95). In a finding consistent with earlier reports, progression-free survival was longer in the doxorubicin-trabectedin group (12 months; 95% CI, 10 to 16) than in the doxorubicin group (6 months; 95% CI, 4 to 7); the adjusted hazard ratio for progression or death was 0.37 (95% CI, 0.26 to 0.53). The incidence of adverse events and the percentage of patients with dose reductions were higher with doxorubicin plus trabectedin than with doxorubicin alone. CONCLUSIONS: Combination therapy with doxorubicin and trabectedin induction, followed by trabectedin maintenance, was associated with improved overall survival and progression-free survival, as compared with doxorubicin alone, among patients with metastatic or surgically unresectable uterine or soft-tissue leiomyosarcoma. (Funded by PharmaMar and others; LMS04 ClinicalTrials.gov number, NCT02997358.).
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Protocolos de Quimioterapia Combinada Antineoplásica , Doxorrubicina , Leiomiosarcoma , Neoplasias de los Tejidos Blandos , Trabectedina , Neoplasias Uterinas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Estimación de Kaplan-Meier , Leiomiosarcoma/tratamiento farmacológico , Leiomiosarcoma/mortalidad , Leiomiosarcoma/patología , Quimioterapia de Mantención , Supervivencia sin Progresión , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/patología , Análisis de Supervivencia , Trabectedina/administración & dosificación , Trabectedina/efectos adversos , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/mortalidad , Neoplasias Uterinas/patología , Estadificación de NeoplasiasRESUMEN
Portal vein tumor thrombosis (PVTT) is one of the common complications of HCC and represents a sign of poor prognosis. PVTT signifies advanced liver cancer, deteriorating liver function, and heightened susceptibility to intrahepatic dissemination, systemic metastasis, and complications related to portal hypertension. It is important to seek novel strategies for PVTT arising from HCC. Portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) represents a worse liver function, less treatment tolerance, and poor prognosis. This study aimed to investigate the diagnostic value of the combination of the DeRitis ratio (AST/ALT) and alkaline phosphatase (ALP) index (briefly named DALP) in predicting the occurrence risk of PVTT in patients with HCC. We performed a retrospective study enrolling consecutive patients with HCC from January 2017 to December 2020 in Hebei Medical University Third Hospital. ROC analysis was performed to estimate the predictive effectiveness and optimal cut-off value of DALP for PVTT occurrence in patients with HCC. Kaplan-Meier analysis revealed the survival probabilities in each subgroup according to the risk classification of DALP value. Univariate and multivariate Logistics regression analyses were applied to determine the independent risk for poor prognosis. ROC analysis revealed that the optimal cut-off value for DALP was 1.045, with an area under the curve (AUC) of 0.793 (95% CI 0.697-0.888). Based on the DALP classification (three scores: 0-2) with distinguishable prognoses, patients in the score 0 group had the best prognosis with a 1-year overall survival (OS) of 100%, whereas score 2 patients had the worst prognosis with 1-year OS of 72.4%. Similarly, there was a statistically different recurrence-free survival among the three groups. Besides, this risk classification was also associated with PVTT progression in HCC patients (odds ratio [OR] 5.822, P < 0.0001). Pathologically, patients in the score 2 group had more advanced tumors considering PVTT, extrahepatic metastasis, and ascites than those in score 0, 1 groups. Moreover, patients with a score of 2 had more severe hepatic inflammation than other groups. Combination of DeRitis ratio and ALP index presented a better predictive value for PVTT occurrence in patients with HCC, contributing to the tertiary prevention.
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Fosfatasa Alcalina , Carcinoma Hepatocelular , Neoplasias Hepáticas , Vena Porta , Trombosis de la Vena , Humanos , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/complicaciones , Masculino , Femenino , Vena Porta/patología , Persona de Mediana Edad , Fosfatasa Alcalina/sangre , Estudios Retrospectivos , Pronóstico , Trombosis de la Vena/etiología , Trombosis de la Vena/patología , Trombosis de la Vena/complicaciones , Anciano , Curva ROC , Estimación de Kaplan-MeierRESUMEN
Selenium, a crucial antioxidant in the body, has been linked to all-cause and cause-specific mortality. However, the relationship between selenium and mortality in the general population remains unclear. A total of 5449 participants in the National Health and Nutrition Examination Survey (NHANES) (2003-2004, 2011-2016) were analyzed to track participant mortality until December 31, 2019. The COX proportional hazard model, KaplanâMeier survival analysis and restricted cubic spline regression analysis were used to investigate the associations. Subgroup analysis was conducted on the basis of age (≤ 60, > 60), sex (male, female), and smoking status (nonsmoker, former smoker, and current smoker). The second quartile was associated with lower all-cause mortality and noncardiovascular mortality (HR and 95% CI 0.61,0.45-0.83;0.59,0.42-0.83, respectively). The third quartile was associated with lower cardiovascular-related mortality (HR and 95% CI 0.49, 0.32-0.76). Elevated serum selenium concentrations were associated with lower all-cause mortality, noncardiovascular mortality (range ≤ 129.82 µg/L), and cardiovascular mortality (range ≤ 129.08 µg/L). Subgroup analysis revealed a positive correlation between the serum selenium concentration (range ≥ 129.82 µg/L) and all-cause mortality among the subgroup of current smokers (p < 0.001). This study indicates that the protective effect of the serum selenium concentration on cause-specific mortality decreases beyond a certain range in the general population, potentially increasing the risk of death among current smokers.
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Encuestas Nutricionales , Selenio , Fumar , Humanos , Selenio/sangre , Masculino , Femenino , Persona de Mediana Edad , Fumar/sangre , Estados Unidos/epidemiología , Adulto , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/sangre , Anciano , Causas de Muerte , Modelos de Riesgos Proporcionales , Factores de Riesgo , Estimación de Kaplan-MeierRESUMEN
BACKGROUND: Telomeres are a critical component of chromosome integrity and are essential to the development of cancer and cellular senescence. The regulation of breast cancer by telomere-associated lncRNAs is not fully known, though. The goals of this study were to describe predictive telomere-related LncRNAs (TRL) in breast cancer and look into any possible biological roles for these RNAs. METHODS: We obtained RNA-seq data, pertinent clinical data, and a list of telomere-associated genes from the cancer genome atlas and telomere gene database, respectively. We subjected differentially expressed TRLs to co-expression analysis and univariate Cox analysis to identify a prognostic TRL. Using LASSO regression analysis, we built a prognostic model with 14 TRLs. The accuracy of the model's prognostic predictions was evaluated through the utilization of Kaplan-Meier (K-M) analysis as well as receiver operating characteristic (ROC) curve analysis. Additionally, immunological infiltration and immune drug prediction were done using this model. Patients with breast cancer were divided into two subgroups using cluster analysis, with the latter analyzed further for variations in response to immunotherapy, immune infiltration, and overall survival, and finally, the expression of 14-LncRNAs was validated by RT-PCR. RESULTS: We developed a risk model for the 14-TRL, and we used ROC curves to demonstrate how accurate the model is. The model may be a standalone prognostic predictor for patients with breast cancer, according to COX regression analysis. The immune infiltration and immunotherapy results indicated that the high-risk group had a low level of PD-1 sensitivity and a high number of macrophages infiltrating. In addition, we've discovered a number of small-molecule medicines with considerable for use in treating high-risk groups. The cluster 2 subtype showed the highest immune infiltration, the highest immune checkpoint expression, and the worst prognosis among the two subtypes defined by cluster analysis, which requires more attention and treatment. CONCLUSION: As a possible biomarker, the proposed 14-TRL signature could be utilized to evaluate clinical outcomes and treatment efficacy in breast cancer patients.
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Biomarcadores de Tumor , Neoplasias de la Mama , ARN Largo no Codificante , Telómero , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Femenino , ARN Largo no Codificante/genética , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Telómero/genética , Tasa de Supervivencia , Regulación Neoplásica de la Expresión Génica , Persona de Mediana Edad , Curva ROC , Estudios de Seguimiento , Perfilación de la Expresión Génica , Estimación de Kaplan-MeierRESUMEN
BACKGROUND: Tumor cells (TC) participate in tumor progression by altering the immune responses in the tumor microenvironment. However, the clinical relevance and prognostic effect of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in esophageal squamous cell carcinoma (ESCC) are unknown. The purpose of this study was to investigate the interactions and clinical significance of PD-L1 expression and TILs in ESCC. METHODS: Tissue specimens were collected from 126 patients with ESCC who underwent curative esophagectomy. Immunohistochemical analysis and multiplex immunofluorescence for CD4, CD8, CD25, FOXP3, and PD-L1 in the tumor were used to identify multiple tumor-infiltrating immune cells (TIIC), Tregs, and TC. RESULTS: PD-L1 was expressed in tumor cells (PD-L1 TC). PD-L1 TIIC and PD-L1 TC affected the biological behavior of TC. The positive expression rate of PD-L1 TC and CD8+ TILs was 27.8% (35/126) and 31.7% (40/126), respectively. Kaplan-Meier analysis showed that overall survival (OS) was significantly associated with decreased CD8+ TILs and PD-L1 TC-positive expression, which promote ESCC progression and metastasis. CONCLUSION: Tumor depth, CD8, and PD-L1 TC were independent prognostic factors in ESCC, and a predictive nomogram with these three risk factors improved the accuracy of predicting OS in patients with ESCC after surgical resection. The conjoint analysis of multiple immune-related factors is beneficial for stratifying patient survival risk.
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Antígeno B7-H1 , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Linfocitos Infiltrantes de Tumor , Microambiente Tumoral , Humanos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Antígeno B7-H1/metabolismo , Masculino , Femenino , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/cirugía , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/inmunología , Pronóstico , Persona de Mediana Edad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/inmunología , Anciano , Microambiente Tumoral/inmunología , Biomarcadores de Tumor/metabolismo , Estimación de Kaplan-Meier , Adulto , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , EsofagectomíaRESUMEN
OBJECTIVES: Cancer is a leading cause of death in unhoused adults. We sought to examine the association between housing status, stage at diagnosis and all-cause survival following cancer diagnosis at a public hospital. DESIGN: Retrospective cohort study examining new cancer diagnoses between 1 July 2011 and 30 June 2021. SETTING: A public hospital in San Francisco. EXPOSURE: Housing status (housed, formerly unhoused, unhoused) was ascertained via a county-wide integrated dataset that tracks both observed and reported homelessness. METHODS: We reported univariate analyses to investigate differences in demographic and clinical characteristics by housing group. We then constructed Kaplan-Meier curves stratified by housing group to examine unadjusted all-cause mortality. Finally, we used multivariable Cox proportional hazards models to compare the hazard rate of mortality for each housing status group, adjusting for demographic and clinical factors. RESULTS: Our cohort included 5123 patients with new cancer diagnoses, with 4062 (79%) in housed patients, 623 (12%) in formerly unhoused patients and 438 (9%) in unhoused patients. Unhoused and formerly unhoused patients were more commonly diagnosed with stage 4 disease (28% and 27% of the time, respectively, vs 22% of housed patients). After adjusting for demographic and clinical characteristics, unhoused patients with stage 0-3 disease had a 50% increased hazard of death (adjusted HR (aHR) 1.5, 95% CI 1.1 to 1.9; p<0.004) as did formerly unhoused patients (aHR 1.5, 95% CI 1.2 to 1.9; p=0.001) compared with housed individuals 3 months after diagnosis. CONCLUSIONS: Unhoused and formerly unhoused patients diagnosed with non-metastatic cancer had substantially increased hazards of death compared with housed patients cared for in a public hospital setting. Current or former lack of housing could contribute to poor outcomes following cancer diagnoses via multiple mechanisms.
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Hospitales Públicos , Vivienda , Personas con Mala Vivienda , Neoplasias , Humanos , Femenino , Masculino , Estudios Retrospectivos , Neoplasias/diagnóstico , Neoplasias/mortalidad , Neoplasias/terapia , Persona de Mediana Edad , Hospitales Públicos/estadística & datos numéricos , San Francisco/epidemiología , Personas con Mala Vivienda/estadística & datos numéricos , Anciano , Adulto , Modelos de Riesgos Proporcionales , Estimación de Kaplan-MeierRESUMEN
BACKGROUND: Despite evidence indicating the dominance of cell-of-origin signatures in molecular tumor patterns, translating these genome-wide patterns into actionable insights has been challenging. This study introduces breast cancer cell-of-origin signatures that offer significant prognostic value across all breast cancer subtypes and various clinical cohorts, compared to previously developed genomic signatures. METHODS: We previously reported that triple hormone receptor (THR) co-expression patterns of androgen (AR), estrogen (ER), and vitamin D (VDR) receptors are maintained at the protein level in human breast cancers. Here, we developed corresponding mRNA signatures (THR-50 and THR-70) based on these patterns to categorize breast tumors by their THR expression levels. The THR mRNA signatures were evaluated across 56 breast cancer datasets (5040 patients) using Kaplan-Meier survival analysis, Cox proportional hazard regression, and unsupervised clustering. RESULTS: The THR signatures effectively predict both overall and progression-free survival across all evaluated datasets, independent of subtype, grade, or treatment status, suggesting improvement over existing prognostic signatures. Furthermore, they delineate three distinct ER-positive breast cancer subtypes with significant survival in differences-expanding on the conventional two subtypes. Additionally, coupling THR-70 with an immune signature identifies a predominantly ER-negative breast cancer subgroup with a highly favorable prognosis, comparable to ER-positive cases, as well as an ER-negative subgroup with notably poor outcome, characterized by a 15-fold shorter survival. CONCLUSIONS: The THR cell-of-origin signature introduces a novel dimension to breast cancer biology, potentially serving as a robust foundation for integrating additional prognostic biomarkers. These signatures offer utility as a prognostic index for stratifying existing breast cancer subtypes and for de novo classification of breast cancer cases. Moreover, THR signatures may also hold promise in predicting hormone treatment responses targeting AR and/or VDR.
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Biomarcadores de Tumor , Neoplasias de la Mama , Receptores Androgénicos , Receptores de Calcitriol , Receptores de Estrógenos , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/metabolismo , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Pronóstico , Receptores de Estrógenos/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica , Estimación de Kaplan-Meier , TranscriptomaRESUMEN
IGFBP6, a member of the IGF binding protein (IGFBP) family, is a specific inhibitor of insulin-like growth factor II (IGF-II) and can inhibit the growth of malignant tumors overexpressing IGF-II. Type 2 diabetes (T2D) is a basic disorder of glucose metabolism that can be regulated by IGF-related pathways. We performed bioinformatics analysis of the TCGA database to explore the possible mechanism of IGFBP6 in breast cancer (BC) metabolism and prognosis and collected clinical samples from BC patients with and without T2D to compare and verify the prognostic effect of IGFBP6. In our study, the levels of IGFBP1-6 were positively correlated with overall survival (OS) in patients with breast cancer. IGFBP6 was upregulated in estrogen receptor (ER)-positive BC, and ER-positive and progesterone receptor (PR) positive patients had a higher expression level of IGFBP6 than ER-negative and PR-negative patients. IGFBP6 could be used as an independent prognostic factor in BC. The expression of IGFBP6 was decreased in BC tissue, and BC tissue from patients with T2D had lower IGFBP6 expression levels than BC tissue from patients without T2D. IGFBP6 is mainly involved in the PI3K-Akt and TGF-ß signaling pathways and tumor microenvironment regulation. In terms of metabolism, the expression of IGFBP6 was negatively correlated with that of most glucose metabolism-related genes. IGFBP6 expression was mainly correlated with mutations in TP53, PIK3CA, CDH1, and MAP3K1. In addition, the upregulation of IGFBP6 in BC increased the drug sensitivity to docetaxel, paclitaxel and gemcitabine. Overall, these results indicated that high expression of IGFBP6 is associated with a good prognosis in BC patients, especially in those without T2D. It is not only involved in the maintenance of the tumor microenvironment in BC but also inhibits the energy metabolism of cancer cells through glucose metabolism-related pathways. These findings may provide a new perspective on IGFBP6 as a potential prognostic marker for BC.
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Biomarcadores de Tumor , Neoplasias de la Mama , Proteína 6 de Unión a Factor de Crecimiento Similar a la Insulina , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Pronóstico , Biomarcadores de Tumor/metabolismo , Proteína 6 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Proteína 6 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Regulación Neoplásica de la Expresión Génica , Biología Computacional/métodos , Transducción de Señal , Glucosa/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Persona de Mediana Edad , Estimación de Kaplan-Meier , Bases de Datos GenéticasRESUMEN
The prognosis of septic patients with cirrhosis is worse compared to septic patients without cirrhosis. Early and accurate prognosis determination in patients with cirrhosis and sepsis is pivotal for guiding treatment decisions. The aim of this study was to investigate the association between albumin-corrected anion gap (ACAG) and clinical prognosis of patients with sepsis and cirrhosis. This study extracted data of patients with sepsis and cirrhosis from the Medical Information Mart for Intensive Care (MIMIC-IV) database. A total of 1340 patients (64.6% male) were enrolled. After confounders adjusting, elevated ACAG had a significant association with 28-day mortality (HR1.604; 95% CI 1.258-2.048; P < 0.001). Restricted cubic spline revealed that a linear relationship between ACAG and 28-day mortality (P-nonlinear = 0.089, P-overall = 0.001). According to the ROC curve analysis, the ACAG demonstrated a higher area under the curve (AUC) of 0.703 compared to AG (0.675). Kaplan-Meier analysis revealed higher 28-day mortality in high ACAG group (log-rank test, χ^2 = 175.638, P < 0.001). Furthermore, subgroup analysis showed a significant interaction between ACAG and etiology of cirrhosis (P for interaction = 0.014). Therefore, ACAG could provide clinicians with valuable insights for guiding interventions in this high-risk population.
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Cirrosis Hepática , Sepsis , Humanos , Cirrosis Hepática/mortalidad , Cirrosis Hepática/complicaciones , Masculino , Femenino , Sepsis/mortalidad , Sepsis/complicaciones , Pronóstico , Persona de Mediana Edad , Anciano , Equilibrio Ácido-Base , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Curva ROC , Estimación de Kaplan-Meier , BiomarcadoresRESUMEN
BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the predominate histological type of renal cell carcinoma (RCC), has been extensively studied, with poor prognosis as the stage increases. Research findings consistently indicated that the PI3K-Akt pathway is commonly dysregulated across various cancer types, including ccRCC. Targeting the PI3K-Akt pathway held promise as a potential therapeutic approach for treating ccRCC. Development and validation of PI3K-Akt pathway-related genes related biomarkers can enhance healthcare management of patients with ccRCC. PURPOSE: This study aimed to identify the key genes in the PI3K-Akt pathway associated with the diagnosis and prognosis of CCRCC using data mining from the Cancer Genome Atlas (TCGA) and Gene Expression Synthesis (GEO) datasets. METHODS: The purpose of this study is to use bioinformatics methods to screen data sets and clinicopathological characteristics associated with ccRCC patients. The exhibited significantly differential expressed genes (DEGs) associated with the PI3K-Akt pathway were examined by KEGG. In addition, Kaplan-Meier (KM) analysis used to estimate the survival function of the differential genes by using the UALCAN database and graphPad Prism 9.0. And exploring the association between the expression levels of the selected genes and the survival status and time of patients with ccRCC based on SPSS22.0. Finally, a multigene prognostic model was constructed to assess the prognostic risk of ccRCC patients. RESULTS: A total of 911 genes with common highly expressed were selected based on the GEO and TCGA databases. According to the KEGG pathway analysis, there were 42 genes enriched in PI3K-Akt signalling pathway. And seven of highly expressed genes were linked to a poor prognosis in ccRCC. And a multigene prognostic model was established based on IL2RG, EFNA3, and MTCP1 synergistic expression might be utilized to predict the survival of ccRCC patients. CONCLUSIONS: Three PI3K-Akt pathway-related genes may be helpful to identify the prognosis and molecular characteristics of ccRCC patients and to improve therapeutic regimens, and these risk characteristics might be further applied in the clinic.
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Biomarcadores de Tumor , Carcinoma de Células Renales , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/mortalidad , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pronóstico , Neoplasias Renales/genética , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Biomarcadores de Tumor/genética , Transducción de Señal/genética , Masculino , Femenino , Biología Computacional , Perfilación de la Expresión Génica , Bases de Datos Genéticas , Persona de Mediana Edad , Estimación de Kaplan-MeierRESUMEN
BACKGROUND: As assessment tools of nutritional status, the controlling nutritional status (CONUT) and modified controlling nutritional status (mCONUT) score are associated with survival in various cancers. We aimed to investigate the association between the CONUT/mCONUT score's prognostic value and survival time in patients with FIGO stage IIB-IIIB cervical cancer treated with radiotherapy. METHODS: In this retrospective study, 165 patients between September 2013 and September 2015 were analyzed, and the optimal CONUT/mCONUT score cut-off values were determined using receiver operating characteristic curves. Propensity score matching (PSM) was used to minimize selection bias. The Kaplan-Meier method and a Cox proportional hazard model were used to assess the CONUT/mCONUT score's predictive value linked to survival time. Two nomograms were created to predict the overall survival (OS) and progression-free survival (PFS). RESULTS: The cut-off values for CONUT and mCONUT score were both 2. Five-year OS and PFS rates were higher in a low CONUT score group than in a high CONUT score group (OS: 81.1% vs. 53.8%, respectively, P < 0.001; PFS: 76.4% vs. 48.2%, respectively; P < 0.001). A high CONUT score was associated with decreased OS (hazard ratio (HR) 2.93, 95% CI 1.54-5.56; P = 0.001) and PFS (HR 2.77, 95% CI 1.52-5.04; P < 0.001). High CONUT scores influenced OS in the PSM cohort. A high mCONUT score was not associated with decreased OS and PFS in Cox regression analysis. CONCLUSION: The CONUT score is a promising indicator for predicting survival in patients with cervical cancer receiving radiotherapy.
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Estado Nutricional , Puntaje de Propensión , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Adulto , Anciano , Estimación de Kaplan-Meier , Nomogramas , Estadificación de Neoplasias , Evaluación Nutricional , Curva ROC , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Circulating tumor cells (CTCs) are pivotal in tumor metastasis across cancers, yet their specific role in renal cancer remains unclear. METHODS: This study investigated C-C motif chemokine ligand 5 (CCL5)'s tumorigenic impact on renal cancer cells and CTCs using bioinformatics, in vivo, and in vitro experiments. It also assessed renal cancer patients' CTCs prognostic value through Lasso regression and Kaplan-Meier survival curves. RESULTS: Bioinformatics analysis revealed differential genes focusing on cellular adhesion and migration between CTCs and tumor cells. CCL5 exhibited high expression in various CTCs, correlating with poor prognosis in renal cancer. In 786-O-CTCs, CCL5 enhanced malignancy, while in renal cell carcinoma cell line CAKI-2 and 786-O, it promoted epithelial-mesenchymal transition (EMT) via smad2/3, influencing cellular characteristics. The nude mouse model suggested CCL5 increased CTCs and intensified EMT, enhancing lung metastasis. Clinical results shown varying prognostic values for different EMT-typed CTCs, with mesenchymal CTCs having the highest value. CONCLUSIONS: In summary, CCL5 promoted EMT in renal cancer cells and CTCs through smad2/3, enhancing the malignant phenotype and facilitating lung metastasis. Mesenchymal-type CTC-related factors can construct a risk model for renal cancer patients, allowing personalized treatment based on metastatic risk prediction.
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Quimiocina CCL5 , Transición Epitelial-Mesenquimal , Neoplasias Renales , Ratones Desnudos , Células Neoplásicas Circulantes , Transición Epitelial-Mesenquimal/genética , Quimiocina CCL5/metabolismo , Humanos , Células Neoplásicas Circulantes/patología , Células Neoplásicas Circulantes/metabolismo , Animales , Línea Celular Tumoral , Neoplasias Renales/patología , Neoplasias Renales/sangre , Neoplasias Renales/genética , Pronóstico , Masculino , Regulación Neoplásica de la Expresión Génica , Femenino , Estimación de Kaplan-Meier , Ratones , Movimiento Celular , Persona de Mediana EdadRESUMEN
BACKGROUND: For treating recurrent glioblastoma, for which there is no established treatment, the antiangiogenic antibody, bevacizumab, is used alone or with irinotecan. This study was aimed at comparing the survival of patients with recurrent glioblastoma receiving bevacizumab monotherapy and those receiving bevacizumab plus irinotecan combination therapy (B+I) by using a nationwide population-based dataset. METHODS: Patients matching the International Classification of Diseases code C71.x were screened from the Health Insurance Review and Assessment Service database. From January 2008 to November 2021, patients who underwent surgery or biopsy and subsequent standard concurrent chemoradiation with temozolomide were included. Among them, those who received bevacizumab monotherapy or B+I were selected. Demographic characteristics, inpatient stay, prescription frequency, survival outcomes, and steroid prescription duration were compared between these two groups. RESULTS: Eight hundred and forty-six patients who underwent surgery or biopsy and received concurrent chemoradiotherapy with temozolomide were included. Of these, 450 and 396 received bevacizumab monotherapy and B+I, respectively. The corresponding median overall survival from the initial surgery was 22.60 months (95% confidence interval [CI], 20.50-24.21) and 20.44 months (95% CI, 18.55-22.60; P = 0.508, log-rank test). The B+I group had significantly more bevacizumab prescriptions (median 5 times; BEV group: median 3 times). Cox analysis, based on the postsurgery period, revealed that male sex (hazard ratio [HR], 1.28; P = 0.002), older age (HR, 1.01; P = 0.042), and undergoing biopsy instead of surgery (HR, 1.79; P < 0.0001) were significantly associated with decreased survival. Fewer radiotherapy cycles correlated with improved survival outcomes (HR, 0.63; P = 0.001). Cox analysis, conducted from the start of chemotherapy including bevacizumab, showed that male sex was the only variable significantly associated with decreased survival (HR, 1.18; P = 0.044). CONCLUSION: We found no significant difference in overall survival between the bevacizumab monotherapy and B+I groups. Considering the additional potential toxicity associated with irinotecan, bevacizumab monotherapy could be a suitable treatment option for treating recurrent glioblastoma.