前列腺纤维性增生的差异表达基因筛选及富集研究

Screening and identification of differentially expressed genes in benign prostatic fibrous hyperplasia and the enrichment analysis

摘要:

目的 筛选和初步鉴定良性前列腺纤维性增生的差异表达基因（DEGs），发现新的良性前列腺纤维性增生的基因片段，为临床监测和治疗前列腺纤维性增生提供潜在的基因位点和标志物依据。方法 收集前列腺等离子电切术后组织标本，根据标本病理诊断结果，将标本分成纤维组和结节组。标本冷冻保存，分别提取前列腺结节性增生标本和纤维性增生标本的组织总RNA，构建转录组文库，通过二代高通量测序，对两组mRNA进行定量及差异分析，再做差异基因的GO、KEGG、网络互作分析。结果 两组标本总共发现差异表达基因1 598个，与结节组相比，纤维组相对表达量上调基因1 063个，相对表达量下调基因535个。通过GO富集分析发现，DGEs主要富集在离子转运、细胞黏附、细胞外基质组等生物学过程中，富集在近端启动子DNA结合转录激活剂、RNA聚合酶Ⅱ、DNA结合转录激活剂、信号受体结合等活性分子功能上，以及富集在细胞膜、细胞外区域、质膜等细胞部位。KEGG通路分析发现，DGEs主要富集在细胞外基质-受体作用、细胞因子与细胞因子受体作用等信号通路上。构建DEGs的PPI网络互作筛选出10个重要基因，发现PPBP、OPRM1、GAL 3个基因在前列腺纤维性增生组织中上调。结论 PPBP、OPRM1、GAL等DEGs参与前列腺纤维性增生的发生、发展，可能是良性前列腺纤维性增生监测和治疗的潜在分子标志物。

Abstract:

Objective To screen and preliminarily identify differentially expressed genes (DEGs) in benign prostatic fibrous hyperplasia, and to discover novel gene fragments involved in the occurrence of benign prostatic fibrous hyperplasia, thereby providing potential target gene loci and biomarkers for the diagnosis and treatment of benign prostatic fibrous hyperplasia.Methods Prostate tissues were collected from 14 patients after transurethral plasma kinetic prostatectomy. According to the pathological diagnosis, all the specimens were divided into fibrous group and nodular group. The specimens were cryopreserved, and the total RNA was extracted respectively to construct a transcriptome library. Through the second-generation high-throughput sequencing, the mRNA in the two groups was quantified and the DEGs between the groups were determined. Then Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) analyses based on the DEGs were carried out.Results A total of 1598 DEGs were found between the two groups. As compared with the nodular group, there were 1,063 up-regulated genes and 535 down-regulated genes in the fibrous group. The GO functional enrichment analysis showed that DEGs were enriched in biological processes such as the ion transport, cellular adhesion, and extracellular matrix organization, molecular functions such as the proximal promoter DNA-binding transcription activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding, DNA-binding transcription activator activity, and signaling receptor binding, and cellular components such as integral component of membrane, extracellular region, and plasma membrane. In addition, KEGG pathway analysis exhibited that DEGs were mainly enriched in extracellular matrix-receptor interaction and cytokine-cytokine receptor interaction. The construction of PPI network of DEGs identified 10 hub genes and found that PPBP, OPRM1 and GAL were up-regulated in benign prostatic fibrous hyperplasia.Conclusions PPBP, OPRM1, GAL and other DEGs are involved in the occurrence and development of benign prostatic fibrous hyperplasia, and can be established as potential biomarkers for treating benign prostatic fibrotic hyperplasia and monitoring the disease activity.