Histone lactatation-related genes GPR19 and SLC22A16 are important diagnostic markers and drug treatment targets for prostate cancer.

Abstract

Background: Histone lactylation is an emerging epigenetic modification involved in tumor progression, but its transcriptional characteristics and clinical relevance in prostate cancer (PCa) remain poorly understood.

Purpose: To preliminarily explore histone lactylation-related transcriptional features in prostate cancer and identify potential diagnostic biomarkers.

Methods: The TCGA-PRAD dataset was used as the training cohort and the GSE46602 dataset as the validation cohort. Based on histone lactylation-related genes (HLRGs) reported in the literature, single-sample gene set enrichment analysis (ssGSEA) scores were calculated to characterize histone lactylation-related transcriptional states. Differentially expressed genes were identified between tumor and normal tissues, as well as between highand low-ssGSEA score groups, and overlapping genes were selected for further analysis. Mendelian randomization (MR) analysis was then applied to identify genes significantly associated with PCa, and receiver operating characteristic (ROC) curves were used to evaluate their discriminatory performance. Functional enrichment and regulatory network analyses were also performed. In addition, gene expression was examined in prostate-related cell lines, and gene knockdown experiments were conducted to preliminarily assess the effects on prostate cancer cell viability and proliferation.

Results: GPR19 and SLC22A16 were ultimately identified as candidate biomarkers. Both genes were significantly upregulated in prostate cancer tissues and cell lines. Functional analyses indicated that GPR19 and SLC22A16 were associated with the "cell cycle" and "aminoacyl-tRNA biosynthesis" pathways, respectively. In vitro experiments showed that knockdown of SLC22A16 significantly suppressed the viability and proliferation of PC-3 cells.

Conclusion: Based on histone lactylation-related transcriptional features, this study preliminarily identified GPR19 and SLC22A16 as genes associated with prostate cancer and provided supportive evidence for their potential biological relevance. Further studies are required to elucidate their regulatory mechanisms and clinical significance.