Identification of Putative Therapeutic Targets of Prostate Cancer Using Integrated Analysis of Microarray and RNA-Seq Analyses

Abstract

Prostate cancer (PCa) is a fatal disease involving abnormal growth and unequal division of cells in prostate gland. PCa is a most frequently diagnosed malignancy around the globe. Previously, some therapeutic targets associated with PCa have been identified that are used in different therapies of PCa but still the disease cannot be cured completely requiring more exploration of the disease pathogenesis at molecular level and development of more effective therapeutic regimens. Therefore, the purpose of this research was to study prostate cancer at molecular level and to identify putative therapeutic targets of PCa through integration of microarray and RNA-Seq data analysis following systems biology approaches that would help to improve PCa treatment efficacy. To achieve this purpose in our research microarray and RNA-Seq datasets of PCa had been analyzed using computational and statistical methods through which differentially expressed genes (DEGs) were identified in order to differentiate between normal and PCa patients. Then, role of DEGs in PCa was investigated through pathways analysis and gene set enrichment analysis. Afterwards, putative therapeutic targets of PCa were evaluated using network analysis. In result of this research some common pathways linked to all the datasets DEGs were obtained including focal adhesion, vascular smooth muscle contraction, proteoglycans in cancer, prostate cancer pathway, pathways in cancer, apoptosis, PI3K-Akt signaling pathway, MAPK signaling pathway, cGMP-PKG signaling pathway, oxytocin signaling pathway, Ras signaling pathway, AMPK signaling pathway, p53 signaling pathway, adherens junction, cell adhesion molecules, human papillomavirus infection and Epstein-Barr virus infection. All these pathways have critical role in the development and progression of prostate cancer. Besides, through network analysis of DEGs, 26 hub genes were identified that are VCL,ACTA2, TPM1, ACTN1, TPM2, MYLK, MYH11, CALD1, FLNA, MYL9, SSB, HNRNPC, RPL7A, LARP7, CCT8, MLLT4, TXNRD1, CTNNA1, ARHGDIB, TROVE2, CAV1, GSN, 1 Abstract SVIL, FLNC, VIM, PARVA. These genes are highly differentially expressed in PCa samples in our analysis and have crucial roles in PCa therefore, can be used as putative therapeutic targets in PCa treatment regimens. Moreover, hub genes; VCL, FLNA, CAV1, GSN, ACTN1, TPM1, SVIL, FLNC, VIM, PARVA, are cell surface DEGs therefore, these can be used as potential immunotherapeutic targets of PCa.