[Identification of prognostic genes in prostate cancer by single-cell sequencing combined with Mendelian randomization].

OBJECTIVETo identify the key genes involved in the development and progression of prostate cancer (PCa) and those associated with the prognosis of the malignancy.

METHODSWe obtained the single-cell sequencing data on 4 cases of PCa from the GSE156632 database. Using R language and the Seurat package, we performed cell clustering and annotation, selected the subpopulations of epithelial cells for differential analysis after quality control and cell type identification, and conducted enrichment analysis of the identified differential genes using the Hiplot website. Then we downloaded the single nucleotide polymorphism (SNP) loci corresponding to the expression quantitative trait loci (eQTL) of these genes from the UK Biobank (UKB) database, and the clinical data and corresponding gene expression data on PCa patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), followed by univariate COX regression analysis of the impact of the genes on the prognosis of the patients after Mendelian randomization.

RESULTSA total of 1 566 genes were identified and subjected to enrichment analysis, which indicated that the differential genes might be enriched in the Ras, apoptosis and oxidative phosphorylation signaling pathways. Subsequent Mendelian randomization revealed 74 potential causal genes among the 1 566 genes, and univariate COX regression analysis of the 74 genes identified 4 possibly related genes FAM3B, JUNB, TMEM59, and KRT5. Comparison of the results of Mendelian randomization and univariate COX regression showed that KRT5 might be the most important gene influencing PCa.

CONCLUSIONFAM3B, JUNB, TMEM59 and KRT5 may play a role in the progression of PCa, and KRT5 may potentially serve as a prognostic predictor and therapeutic target for the malignancy.