IntroductionProstate cancer is a common cancer among male population. The aberrant expression of histone modifiers has been identified as a potential driving force in numerous cancer types. However, the mechanism of histone modifiers in the development of prostate cancer remains unknown.MethodsExpression profiles and clinical data were obtained from GSE70769, GSE46602, and GSE67980. Seruat R package was utilized to calculate the gene set enrichment of the histone modification pathway and obtain the Histone score. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were employed to identify marker genes with prognostic value. Kaplan–Meier survival analysis was conducted to assess the efficacy of the prognostic model. In addition, microenvironment cell populations counter (MCPcounter), single‐sample gene set enrichment analysis (ssGSEA), and xCell algorithms were employed for immune infiltration analysis. Drug sensitivity prediction was performed using oncoPredict R package.ResultsWe screened differentially expressed genes (DEGs) between Histone‐high score (Histone‐H) and Histone‐low score (Histone‐L) groups, which were enriched in RNA splicing and DNA‐binding transcription factor binding pathways. We retained four prognostic marker genes, including TACC3, YWHAH, TAF1C and TTLL5. The risk model showed significant efficacy in stratification of the prognosis of prostate cancer patients in both internal and external cohorts (p < .0001 and p = .032, respectively). In addition, prognostic gene YWHAH was infiltrated in abundance of fibroblasts and highly correlated with Entinostat_1593 drug sensitivity score and the value of risk score.ConclusionWe innovatively developed a histone modification‐related prognostic model with high prognostic potency and identified YWHAH as possible diagnostic and therapeutic biomarkers for prostate cancer. It provides novel insights to address prostate cancer and enhance clinical outcomes, thereby opening up a new avenue for customized treatment alternatives.
BackgroundLocally advanced breast cancer (LABC) is generally considered to have a relatively poor prognosis. However, with years of follow-up, what is its real-time survival and how to dynamically estimate an individualized prognosis? This study aimed to determine the conditional survival (CS) of LABC and develop a CS-nomogram to estimate overall survival (OS) in real-time.MethodsLABC patients were recruited from the Surveillance, Epidemiology, and End Results (SEER) database (training and validation groups, n = 32,493) and our institution (testing group, n = 119). The Kaplan–Meier method estimated OS and calculated the CS at year (x+y) after giving x years of survival according to the formula CS(y|x) = OS(y+x)/OS(x). y represented the number of years of continued survival under the condition that the patient was determined to have survived for x years. Cox regression, best subset regression, and the least absolute shrinkage and selection operator (LASSO) regression were used to screen predictors, respectively, to determine the best model to develop the CS-nomogram and its network version. Risk stratification was constructed based on this model.ResultsCS analysis revealed a dynamic improvement in survival occurred with increasing follow-up time (7 year survival was adjusted from 63.0% at the time of initial diagnosis to 66.4, 72.0, 77.7, 83.5, 89.0, and 94.7% year by year [after surviving for 1–6 years, respectively]). In addition, this improvement was non-linear, with a relatively slow increase in the second year after diagnosis. The predictors identified were age, T and N status, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER 2), surgery, radiotherapy and chemotherapy. A CS-nomogram developed by these predictors and the CS formula was used to predict OS in real-time. The model's concordance indexes (C-indexes) in the training, validation and testing groups were 0.761, 0.768 and 0.810, which were well-calibrated according to the reality. In addition, the web version was easy to use and risk stratification facilitated the identification of high-risk patients.ConclusionsThe real-time prognosis of LABC improves dynamically and non-linearly over time, and the novel CS-nomogram can provide real-time and personalized prognostic information with satisfactory clinical utility.
BackgroundSurvival prediction for cervical cancer is usually based on its stage at diagnosis or a multivariate nomogram. However, few studies cared whether long-term survival improved after they survived for several years. Meanwhile, traditional survival analysis could not calculate this dynamic outcome. We aimed to assess the improvement of survival over time using conditional survival (CS) analysis and developed a novel conditional survival nomogram (CS-nomogram) to provide individualized and real-time prognostic information.MethodsCervical cancer patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan–Meier method estimated cancer-specific survival (CSS) and calculated the conditional CSS (C-CSS) at year y+x after giving x years of survival based on the formula C-CSS(y|x) =CSS(y+x)/CSS(x). y indicated the number of years of further survival under the condition that the patient was determined to have survived for x years. The study identified predictors by the least absolute shrinkage and selection operator (LASSO) regression and used multivariate Cox regression to demonstrate these predictors’ effect on CSS and to develop a nomogram. Finally, the CSS possibilities predicted by the nomogram were brought into the C-CSS formula to create the CS-nomogram.ResultsA total of 18,511 patients aged <65 years with cervical cancer from 2004 to 2019 were included in this study. CS analysis revealed that the 15-year CSS increased year by year from the initial 72.6% to 77.8%, 84.5%, 88.8%, 91.5%, 93.5%, 94.8%, 95.7%, 96.4%, 97.3%, 98.0%, 98.5%, 99.1%, and 99.4% (after surviving for 1-13 years, respectively), and found that when survival exceeded 5-6 years, the risk of death from cervical cancer would be less than 5% in 10-15 years. The CS-nomogram constructed using tumor size, lymph node status, distant metastasis status, and histological grade showed strong predictive performance with a concordance index (C-index) of 0.805 and a stable area under the curve (AUC) between 0.795 and 0.816 over 15 years.ConclusionsCS analysis in this study revealed the gradual improvement of CSS over time in long-term survived cervical cancer patients. We applied CS to the nomogram and developed a CS-nomogram successfully predicting individualized and real-time prognosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.