Radiotherapy effects on the ceRNA network in high-risk prostate cancer patients

Radiotherapy (RT) dramatically reduces the risk of prostate cancer (PCa) recurrence and extends patient lifespans. Recent studies have begun identifying gene signatures and biomarkers that may predict and monitor RT responses. Hence, we investigated the effects of radiotherapy (RT) on competing endogenous RNA (ceRNA) networks, including long non-coding rinonucleic acid (lncRNA), microRNA (miRNA), and messenger RNA (mRNA), in high-risk prostate cancer (HrPCa) patients.

The Gene Expression Omnibus (GEO) database was used to identify mRNAs with significant expression differences. The analysis largely followed the packages outlined in GEO2R. The TargetScan, miRanda, and LncRNA2Target databases were utilized to identify lncRNAs and miRNAs. Protein-protein interactions identified hub genes, and Gene Ontology terms revealed their critical pathways. Finally, 28 patients with HrPCa and 28 healthy subjects were included in the study. Whole blood samples were collected from all participants before and after RT. RNA extraction and cDNA synthesis were then performed, followed by real-time polymerase chain reaction (PCR) to determine the expression of candidate biomarkers. Due to the small sample size (n = 28), Hedges' g was used instead of Cohen's d to minimize bias.

We identified 3,452 genes, including 1,951 up-regulated and 1,501 down-regulated genes, exhibiting significant differential expression in patients with HrPCa. Ultimately, three lncRNAs, seven miRNAs, and nine mRNAs were selected as candidates for comparison between HrPCa patients and healthy subjects. Unlike a significant increase in tumor suppressors, the expression levels of candidate onco-miRNAs, onco-lncRNAs, and oncogenes in HrPCa patients showed a substantial decrease after RT.

The ceRNA network monitoring might be emerging as a valuable tool for assessing treatment responses. However, future studies with larger cohorts are needed to validate these results.