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.
