LncRNA Weighted Gene Co-expression Network Analysis Reveals Novel Biomarkers Related to Prostate Cancer Metastasis

Overview

Journal BMC Med Genomics

Publisher Biomed Central

Specialty Genetics

Date 2022 Dec 13

PMID 36514044

Authors

Miao Liu

Man-Yun Chen

Jia-Meng Huang

Qian Liu

Lin Wang

Rong Liu

Nian Yang

Wei-Hua Huang

Wei Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Most prostate cancer patients die from metastasis and lack accurate efficacious biomarkers to monitor the disease behavior, optimize treatment and assess prognosis. Herein, we aimed to identify meaningful lncRNA biomarkers associated with prostate cancer metastatic progression.

Methods: By repurposing microarray probes, 11,624 lncRNAs in prostate cancer were obtained from Gene Expression Omnibus database (GSE46691, N = 545; GSE29079, N = 235; GSE94767, N = 130). Weighted gene co-expression network analysis was applied to determine the co-expression lncRNA network pertinent to metastasis. Hub lncRNAs were screened. RNA-seq and clinical data from the Cancer Genome Atlas prostate cancer (TCGA-PRAD) cohort (N = 531) were analyzed. Transwell assay and bioinformatic analysis were performed for mechanism research.

Results: The high expression levels of nine hub lncRNAs (FTX, AC005261.1, NORAD, LINC01578, AC004542.2, ZFAS1, EBLN3P, THUMPD3-AS1, GAS5) were significantly associated with Gleason score and increased probability of metastatic progression. Among these lncRNAs, ZFAS1 had the consistent trends of expression in all of the analysis from different cohorts, and the Kaplan-Meier survival analyses showed higher expression of ZFAS1 was associated with shorter relapse free survival. In-vitro studies confirmed that downregulation of ZFAS1 decreased prostate cancer cell migration.

Conclusion: We offered some new insights into discovering lncRNA markers correlated with metastatic progression of prostate cancer using the WGCNA. Some may serve as potential prognostic biomarkers and therapeutic targets for advanced metastatic prostate cancer.

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