4.6 Article

Comprehensive Analysis of Cell Cycle-Related Genes in Patients With Prostate Cancer

Journal

FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.796795

Keywords

prostate cancer; GSVA; cell cycle; recurrence-free survival; immunotherapy

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This study aimed to identify critical cell cycle-related genes in prostate cancer and evaluate their clinical prognostic value. The researchers found that cell cycle-related pathways play important roles in prostate cancer. By analyzing gene expression data and using survival analysis methods, nine genes associated with patient prognosis were identified. A risk scoring model was constructed using these genes and validated in clinical datasets. Additionally, functional enrichment analysis and mutation profiling were conducted to explore the biological characteristics and potential drug targets of these genes.
This study aimed to identify critical cell cycle-related genes (CCRGs) in prostate cancer (PRAD) and to evaluate the clinical prognostic value of the gene panel selected. Gene set variation analysis (GSVA) of dysregulated genes between PRAD and normal tissues demonstrated that the cell cycle-related pathways played vital roles in PRAD. Patients were classified into four clusters, which were associated with recurrence-free survival (RFS). Moreover, 200 prognostic-related genes were selected using the Kaplan-Meier (KM) survival analysis and univariable Cox regression. The prognostic CCRG risk score was constructed using random forest survival and multivariate regression Cox methods, and their efficiency was validated in Memorial Sloan Kettering Cancer Center (MSKCC) and GSE70770. We identified nine survival-related genes: CCNL2, CDCA5, KAT2A, CHTF18, SPC24, EME2, CDK5RAP3, CDC20, and PTTG1. Based on the median risk score, the patients were divided into two groups. Then the functional enrichment analyses, mutational profiles, immune components, estimated half-maximal inhibitory concentration (IC50), and candidate drugs were screened of these two groups. In addition, the characteristics of nine hub CCRGs were explored in Oncomine, cBioPortal, and the Human Protein Atlas (HPA) datasets. Finally, the expression profiles of these hub CCRGs were validated in RWPE-1 and three PRAD cell lines (PC-3, C4-2, and DU-145). In conclusion, our study systematically explored the role of CCRGs in PRAD and constructed a risk model that can predict the clinical prognosis and immunotherapeutic benefits.

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