Di Longjiang, Gu Maoli, Wu Yan, Liu Guoqiang, Zhang Lishuo, Li Yifei, Zhang Wenjing
Department of Clinical Laboratory, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang, China.
Department of Urology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang, China.
Cancer Cell Int. 2022 Apr 7;22(1):144. doi: 10.1186/s12935-022-02558-2.
Prostate cancer (PCa) is one of the most lethal cancers in male individuals. The synaptosome associated protein 25 (SNAP25) gene is a key mediator of multiple biological functions in tumors. However, its significant impact on the prognosis in PCa remains to be elucidated.
We performed a comprehensive analysis of the Cancer Genome Atlas dataset (TCGA) to identify the differentially expressed genes between PCa and normal prostate tissue. We subjected the differentially expressed genes to gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes functional analysis, and constructed a protein-protein interaction network. We then screened for pivotal genes to identify the hub genes of prognostic significance by performing Cox regression analysis. We identified SNAP25 as one such gene and analyzed the relationship between its expression in PCa to poor prognosis using GEPIA interactive web server.
TCGA database demonstrated that SNAP25 was significantly downregulated in PCa. The progressive decrease in SNAP25 expression with the increase in the clinical staging and grading of PCa demonstrates that reduced SNAP25 expression considerably exacerbates the clinical presentation. Our findings confirm that SNAP25 expression strongly correlates with overall survival, which was determined using the Gleason score. We also validated the role of SNAP25 expression in the prognosis of patients with PCa. We used Gene Set Enrichment and Gene Ontology analyses to evaluate the function of SNAP25 and further explored the association between SNAP25 expression and tumor-infiltrating immune cells using the Tumor Immune Assessment Resource database. We found for the first time that SNAP25 is involved in the activation, differentiation, and migration of immune cells in PCa. Its expression was positively correlated with immune cell infiltration, including B cells, CD8 T cells, CD4 T cells, neutrophils, dendritic cells, macrophages, and natural killer cells. SNAP25 expression also positively correlated with chemokines/chemokine receptors, suggesting that SNAP25 may regulate the migration of immune cells. In addition, our experimental results verified the low expression of SNAP25 in PCa cells.
Our findings indicate a relationship between SNAP25 expression and PCa, demonstrating that SNAP25 is a potential prognostic biomarker due to its vital role in immune infiltration.
前列腺癌(PCa)是男性中最致命的癌症之一。突触体相关蛋白25(SNAP25)基因是肿瘤中多种生物学功能的关键调节因子。然而,其对PCa预后的显著影响仍有待阐明。
我们对癌症基因组图谱数据集(TCGA)进行了全面分析,以确定PCa与正常前列腺组织之间的差异表达基因。我们对差异表达基因进行了基因本体分析和京都基因与基因组百科全书功能分析,并构建了蛋白质-蛋白质相互作用网络。然后,我们通过进行Cox回归分析筛选关键基因,以鉴定具有预后意义的枢纽基因。我们确定SNAP25就是这样一个基因,并使用GEPIA交互式网络服务器分析了其在PCa中的表达与不良预后之间的关系。
TCGA数据库显示,SNAP25在PCa中显著下调。随着PCa临床分期和分级的增加,SNAP25表达逐渐降低,这表明SNAP25表达降低会显著加重临床表现。我们的研究结果证实,SNAP25表达与总生存期密切相关,总生存期是使用Gleason评分确定的。我们还验证了SNAP25表达在PCa患者预后中的作用。我们使用基因集富集分析和基因本体分析来评估SNAP25的功能,并使用肿瘤免疫评估资源数据库进一步探索SNAP25表达与肿瘤浸润免疫细胞之间的关联。我们首次发现SNAP25参与了PCa中免疫细胞的激活、分化和迁移。其表达与免疫细胞浸润呈正相关,包括B细胞、CD8 T细胞、CD4 T细胞、中性粒细胞、树突状细胞、巨噬细胞和自然杀伤细胞。SNAP25表达也与趋化因子/趋化因子受体呈正相关,表明SNAP25可能调节免疫细胞的迁移。此外,我们的实验结果证实了PCa细胞中SNAP25的低表达。
我们的研究结果表明SNAP25表达与PCa之间存在关联,表明SNAP25因其在免疫浸润中的重要作用而成为一种潜在的预后生物标志物。