Abstract

BackgroundProstate cancer (PC) is a commonly diagnosed malignancy in males, especially in the western hemisphere. The extensive use of multiple biomarkers plays an important role in the diagnosis and prognosis of PC. However, the accuracy of biomarkers for PC prognosis needs to be urgently improved. This study aimed to identify a novel prognostic biomarker for PC.Materials and methodsDifferentially methylated CpG sites were identified from the GSE76938 dataset (https://www.ncbi.nlm.nih.gov/geo/) using R software version 3.1.4. Four significant CpG sites on the SLCO4C1 gene were found to be closely associated with prognosis in PC. Data downloaded from The Cancer Genome Atlas (TCGA) were used for validation. Co-expression and functional enrichment analyses were used to explore the roles of SLCO4C1 in molecular functions, biological processes and cellular components. Total RNA extraction and qRT-PCR were used to reveal the difference in SLCO4C1 expression between tumour and normal tissues. Bisulfite amplicon sequencing (BSAS) was used to identify methylation levels at the CpG sites.ResultsIn the GSE76938 cohort, 10,206 CpG sites were identified to be differentially methylated in tumour versus normal prostate tissues. Among the CpG sites, four sites (cg06480736, cg19774478, cg19788741 and cg22149516) located in the promotor region (TSS200-1500) of SLCO4C1 were found to be significantly hypermethylated in tumour tissues. The results were validated in an independent dataset (TCGA PRAD cohort). In the cohort from TCGA, SLCO4C1 expression was negatively correlated with methylation levels at the four sites. The results of qRT-PCR validated that tumour tissues had a relatively lower expression of SLCO4C1. Bisulfite amplicon sequencing (BSAS) further confirmed a higher methylation level at the SLCO4C1 promoter in tumour tissues. SLCO4C1 (cg06480736, cg19774478, cg19788741 and cg22149516) was identified as a significant promising biomarker for biochemical recurrence-free survival in Kaplan-Meier analysis (P < 0.01) and univariate Cox proportional hazards analysis: cg06480736 (HR 15.914, P < 0.001), cg19774478 (HR 9.001, P < 0.001), cg19788741 (HR 10.759, P = 0.003) and cg22149516 (HR 17.144, P = 0.006). However, three sites, namely, cg06480736 (HR 1.809, P = 0.049), cg19774478 (HR 1.903, P = 0.041) and cg22149516 (HR 2.316, P = 0.008), were confirmed in multivariate analysis.ConclusionsSLCO4C1 promoter methylation, including that at three CpG sites, namely, cg06480736, cg19774478 and cg22149516, is a potential biomarker for risk stratification and might offer significantly relevant prognostic information for PC patients after radical prostatectomy.

Highlights

  • Prostate cancer (PC) is a commonly diagnosed malignancy in males, especially in the western hemisphere

  • SLCO4C1 promoter had higher methylation levels in PC tissues and the gene transcription was decreased from the Gene Expression Omnibus (GEO) database For the exploration of significant methylation sites in prostate cancer tissues, the GSE76938 dataset, including

  • SLCO4C1 significantly influenced biological processes The top 100 genes co-expressed with SLCO4C1 selected from PC profiles in The Cancer Genome Atlas (TCGA) database were included in WebGestalt to perform gene ontology analysis

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Summary

Introduction

Prostate cancer (PC) is a commonly diagnosed malignancy in males, especially in the western hemisphere. The extensive use of multiple biomarkers plays an important role in the diagnosis and prognosis of PC. Prostate cancer (PC) is a common malignancy in males, especially in the western hemisphere. PC accounts for 9.9% of all new tumors [1]. This disease has become a serious threat to the health of elderly men. As a biomarker of prostate cancer, PSA (prostate-specific antigen) plays an important role in early diagnosis. Radical prostatectomy is currently the main curative treatment for prostate cancer. More than 30% of prostate cancer patients experience biochemical recurrence (BCR) after radical prostatectomy within 10 years, and many of these patients may develop metastatic castration-resistant PC (CRPC) [4]

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