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

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...

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Main Authors: Zehua Liu, Rongfang Pan, Wenxian Li, Yanjiang Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.796795/full
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author Zehua Liu
Rongfang Pan
Wenxian Li
Yanjiang Li
author_facet Zehua Liu
Rongfang Pan
Wenxian Li
Yanjiang Li
author_sort Zehua Liu
collection DOAJ
description 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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spelling doaj.art-f417b0159e31407cb7bad823426d2adf2022-12-21T19:48:33ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-01-011110.3389/fonc.2021.796795796795Comprehensive Analysis of Cell Cycle-Related Genes in Patients With Prostate CancerZehua Liu0Rongfang Pan1Wenxian Li2Yanjiang Li3Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Nutrition, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Urology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Urology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaThis 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.796795/fullprostate cancerGSVAcell cyclerecurrence-free survivalimmunotherapy
spellingShingle Zehua Liu
Rongfang Pan
Wenxian Li
Yanjiang Li
Comprehensive Analysis of Cell Cycle-Related Genes in Patients With Prostate Cancer
Frontiers in Oncology
prostate cancer
GSVA
cell cycle
recurrence-free survival
immunotherapy
title Comprehensive Analysis of Cell Cycle-Related Genes in Patients With Prostate Cancer
title_full Comprehensive Analysis of Cell Cycle-Related Genes in Patients With Prostate Cancer
title_fullStr Comprehensive Analysis of Cell Cycle-Related Genes in Patients With Prostate Cancer
title_full_unstemmed Comprehensive Analysis of Cell Cycle-Related Genes in Patients With Prostate Cancer
title_short Comprehensive Analysis of Cell Cycle-Related Genes in Patients With Prostate Cancer
title_sort comprehensive analysis of cell cycle related genes in patients with prostate cancer
topic prostate cancer
GSVA
cell cycle
recurrence-free survival
immunotherapy
url https://www.frontiersin.org/articles/10.3389/fonc.2021.796795/full
work_keys_str_mv AT zehualiu comprehensiveanalysisofcellcyclerelatedgenesinpatientswithprostatecancer
AT rongfangpan comprehensiveanalysisofcellcyclerelatedgenesinpatientswithprostatecancer
AT wenxianli comprehensiveanalysisofcellcyclerelatedgenesinpatientswithprostatecancer
AT yanjiangli comprehensiveanalysisofcellcyclerelatedgenesinpatientswithprostatecancer