Identification of key genes and multiple molecular pathways of metastatic process in prostate cancer

Abstract

Background Cancer metastasis is well known as the most adverse outcome and the major cause of mortality in cancer patients, including prostate cancer (PCa). There are no credible predictors, to this day, that can reflect the metastatic ability of localized PCa. In the present study, we firstly identified the differentially expressed genes (DEGs) and molecular pathways involved in the metastaic process of PCa by comparing gene expressions of metastaic PCa with localized PCa directly, with the purpose of identifying potential markers or therapeutic targets. Methods The gene expression profiles (GSE6919 and GSE32269) were downloaded from the Gene Expression Omnibus database, which contained 141 tissue samples, including 87 primary localized PCa samples and 54 metastaic PCa samples. After data processing, DEGs were identified by R language using the Student’s t-test adjusted via the Beniamini–Hochberg method. Subsequently, the gene ontology functional and pathway enrichment analyses of DEGs were performed and the protein–protein interaction network was constructed. Hub genes were identified using the plug-in cytoHubba in Cytoscape software by MCC and degree. Furthermore, validation and prognostic significance analysis of the hub genes were performed by UALCAN and gene expression profiling interactive analysis (GEPIA). Results A total of 90 DEGs were identified between localized and metastaic PCa, which consisted of 47 upregulated and 43 downregulated genes. The enriched functions and pathways of the DEGs include catabolic process, cell cycle, response to steroid hormone, extracellular matrix (ECM)-receptor interaction and vascular smooth muscle contraction. A total of 10 genes were identified as hub genes and biological process analysis of hub genes showed that cell cycle phase, cell division, and mitotic cell cycle process were mainly enriched. The expression of hub genes were confirmed in metastaic PCa when compared with localized PCa tissues by The Cancer Genome Atlas database. Moreover, the disease-free survival analysis of hub genes revealed that these genes may play an important role in invasion, progression or recurrence. Therefore, these hub genes might be the key genes contributed to tumor progression or metastasis in PCa and provide candidate therapeutic targets for PCa. Conclusions The present study identified some DEGs between localized and metastaic PCa tissue samples. These key genes might be potential therapeutic targets and biomarkers for the metastaic process of PCa.

Identification And validation of transcription factor genes involved in prostate cancer metastasis

“…As an integrated analysis based on previous studies, our results showed partial overlap with those previously described. For example, consistent with previous investigations, FOS and FOXM1 were listed in the DEGs between metastatic PCa and localized PCa (Chandran et al 2007;Guo et al 2019). However, differences existed.…”

“…Previous studies reported that different gene expression profiles existed between metastatic PCa and localized PCa either in a single cohort (LaTulippe et al 2002;Varambally et al 2005;Chandran et al 2007;Taylor et al 2010) or in an integrated series (Liu et al 2018;Guo et al 2019;Xu et al 2020).…”

“…Therefore, integrated bioinformatics studies emerge as a solution to address this inadequacy. So far, there have been relatively few integrated bioinformatics studies focusing on comparing gene expression profilings between localized PCa and metastatic PCa (LaTulippe et al 2002;Chandran et al 2007;Liu et al 2018;Guo et al 2019). Besides, most of them contained limited samples or gene expression datasets.…”

Role of methyltransferase-like enzyme 3 and methyltransferase-like enzyme 14 in urological cancers

“…Because of the aging of the growing population, prostate cancer has become a main public health problem for men (Center et al, 2012). This tumor is often silent in clinical practice and usually found after it invades other tissues (Guo et al, 2019;Roobol & Carlsson, 2013;Shen & Abate-Shen, 2010). Studies of METTL3 in prostate cancer suggest that it is a oncogene.…”

Development of a Novel Immune-Related Prognostic Signature for Prostate Cancer

“…Despite initial effective responses with androgen suppression therapy (AST), almost all patients ultimately progress to metastatic castration-resistant prostate cancer (mCRPC) [12,13]. Docetaxel, abiraterone, cabazitaxel, and (Sip-T) are approved by the FDA for the treatment of mCRPC, however each of these regimens provides only limited 2-4 months median survival bene t [14][15][16][17][18].…”