[Identification and validation of hub genes in prostate cancer progression based on weighted gene co-expression network analysis].

Abstract

OBJECTIVE:

To identify the key hub genes in prostate cancer metastasis based on weighted gene co-expression network analysis (WGCNA) and verify the identified genes.

METHODS:

Whole-genome chip data GSE6919 of prostate cancer study were analyzed using principal component analysis (PCA), and the differentially expressed genes (DEGs) were analyzed using R software. WGCNA was performed to construct a gene co-expression network for screening the key genes. TCGA database was used to explore the expressions of the DEGs and their association with the prognosis. To validate the results, we designed siRNA fragments targeting the metastasis-related gene HNRNPA2B1, and observed its effect on growth, apoptosis, clone formation, migration and invasion of prostate cancer cell lines using MTT assay, flow cytometry, clone formation assay, and Transwell assay.

RESULTS:

PCA analysis showed obvious clustering of significant DEGs in metastatic cancer group. The modules obtained by WGCNA analysis in metastasis group involved stem cell differentiation, amino acid metabolism and immune response. Further screening of the genes identified 3 genes related with prostate cancer occurrence (BDH1, PAK4 and EXTL3) and another 3 with prostate cancer metastasis (NKTR, CTBP2 and HNRNPA2B1), which were shown to have differential expressions in TCGA database and were correlated with the patient's overall survival. In the cell experiment, PC3 and LNCap cells transfected with the siRNA fragment targeting HNRNPA2B1 showed obvious growth inhibition with increased cell apoptosis, lowered clone formation ability, and suppressed capacities for migration and invasion.

CONCLUSION:

We identified 3 hub genes related with the occurrence (BDH1, PAK4 and EXTL3) and another 3 with metastasis of prostate cancer (NKTR, CTBP2 and HNRNPA2B1) using WGCNA, which provides a new approach for studying the regulatory mechanisms of prostate cancer.

• Authors: H Zhang, N Chen, X Wang, B Gao, M Ling, G Chen, Z Wu, Y Li, W Zhong, B Pan
• Journal: Nan fang yi ke da xue xue bao = Journal of Southern Medical University (Nan Fang Yi Ke Da Xue Xue Bao) Vol. 41 Issue 11 Pg. 1631-1640 (Nov 20 2021) ISSN: 1673-4254 [Print] China
• PMID: 34916188 (Publication Type: Journal Article)

Chemical References

• Co-Repressor Proteins
• EXTL3 protein, human
• Heterogeneous-Nuclear Ribonucleoprotein Group A-B
• NKTR protein, human
• Receptors, Immunologic
• hnRNP A2
• Alcohol Oxidoreductases
• CTBP2 protein, human
• Hydroxybutyrate Dehydrogenase
• N-Acetylglucosaminyltransferases
• PAK4 protein, human
• p21-Activated Kinases

Topics

• Alcohol Oxidoreductases (genetics)
• Co-Repressor Proteins (genetics)
• Heterogeneous-Nuclear Ribonucleoprotein Group A-B (genetics)
• Humans
• Hydroxybutyrate Dehydrogenase (genetics)
• Male
• N-Acetylglucosaminyltransferases (genetics)
• Prognosis
• Prostatic Neoplasms (genetics)
• Receptors, Immunologic (genetics)
• p21-Activated Kinases (genetics)