Exploring Functional Gene Modules In The Development And Progression Of Prostate Cancer By WGCNA

Prostate cancer is one of the most common malignant tumor in male genitourinary system.Compared to developed countries,the incidence of prostate cancer is lower in China.Whereas,in recent years,the prostate cancer incidence rate in China showed an upward trend.It has become one of the major diseases in middleaged male.Prostate cancer is a complex disease with the pariticipant of multiple genes and multiple factors.Traditional biological research can not reveal the role of DNA,RNA and protein related complex network in the development of prostate cancer.Recently,the generation of massive high-throughput data and application of biological network analysis,such as weighted gene co-expression network,provides a solution for analyzing complex interaction networks from a macroscopic and comprehensive perspective.We performed weighted gene co-expression network analysis methods to construct the risk related network and the progression risk related network.Seven risk modules and a progression risk module were obtained.The seven risk modules are mainly involved in tumor angiogenesis,cell signal transduction,cell cycle and cell repair,m RNA processing,drug metabolism,DNA repair,protein modification,and digestive gland secretion.The progression risk module is mainly involved in cell cycle,cell division and cell repair process.Comparied with the enrichment results of differentially expressed genes,the pathways and biological processes enriched by modules are more specific and detailed,which help us to further our understanding of the specific roles of genes with different expression patterns in cancer.The module with the highest level of risk associated with cancer risk(cor=-0.47)in seven risk modules was enriched in c AMP and calcium channel signaling pathways,suggesting that the disorder of these pathways is closely related to the development of prostate cancer.Gene hub has many lnc RNA,meaning lnc RNA also played an important role in the module.In hub genes with high MM value,RBMS3 and lnc RNA ADAMTS9-AS2 have been documented as a tumor suppressor gene,suggesting that hub genes may have played an important role in the occurrence of prostate cancer in the process.Through the construction of weighted gene network related to the progression of prostate cancer and combination of the clinical progression characteristics,we found that amodule strongly related to tumor invasion.This is highly overlapping to one of the previous risk related module,demonstrating cell cycle and cell division phase imbalance may participated throughout the process of the occurrence and progression of prostate cancer.Its hub genes,such as CENPE,CENPF,NUSAP1 and RACGAP1,have been widely reported to be closely related to the poor out come and invsion and metastasis of cancer.This study shows that by conjoining the the network based coexpression analysis method with clinical sample information we can explore the molecular mechanism of prostate cancer occurrence and development,and find novel potential early molecular markers and potential therapeutic targets.