Ding Junping, Zhao Shubin, Chen Xianhua, Luo Changjun, Peng Jinjian, Zhu Jiantan, Shen Yongqi, Luo Zhou, Chen Jianlin
Departments of Urology of Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, China.
Departments of Clinical Laboratory, Key Laboratory of Medical Molecular Diagnostics of Liuzhou, Key Laboratory for Nucleic Acid Molecular Diagnosis and Application of Guangxi Health & Wellness Commission, Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, China.
Front Genet. 2022 Apr 11;13:835355. doi: 10.3389/fgene.2022.835355. eCollection 2022.
Semaphorin 5B (SEMA5B) has been described to be involved in the development and progression of cancer. However, the potential diagnostic and prognosis roles and its correlation with tumor-infiltrating immune cells in KIRC have not been clearly reported yet. The mRNA level of SEMA5B was analyzed via the TCGA and GTEx database as well as the CCLE dataset and verified by GSE53757 and GSE40435 datasets. Meanwhile, the protein level of SEMA5B was analyzed by CPTAC and validated by HPA. The diagnostic value of SEMA5B was analyzed according to the TCGA database and validated by GSE53757, GSE46699, and GSE11024 + GSE46699 datasets. Then, the survival analysis was conducted using GEPIA2. R software (v3.6.3) was applied to investigate the relevance between SEMA5B and immune checkpoints and m6A RNA methylation regulator expression. The correlation between SEMA5B and MMRs and DNMT expression and tumor-infiltrating immune cells was explored via TIMER2. Co-expressed genes of SEMA5B were assessed by cBioPortal, and enrichment analysis was conducted by Metascape. The methylation analysis was conducted with MEXPRESS and MethSurv online tools. Gene set enrichment analysis (GSEA) was applied to annotate the biological function of SEMA5B. SEMA5B was significantly upregulated at both the mRNA and protein levels in KIRC. Further analysis demonstrated that the mRNA expression of SEMA5B was significantly correlated with gender, age, T stage, pathologic stage, and histologic grade. High levels of SEMA5B were found to be a favorable prognostic factor and novel diagnostic biomarker for KIRC. SEMA5B expression was shown to be significantly associated with the abundance of immune cells in KIRC. Also, SEMA5B expression was significantly correlated with the abundance of MMR genes, DNMTs, and m6A regulators in KIRC. Enrichment analysis indicated that the co-expressed genes may involve in crosslinking in the extracellular matrix (ECM). GSEA disclosed that SYSTEMIC_LUPUS_ERYTHEMATOSUS and NABA_ECM_REGULATORS were prominently enriched in the SEMA5B low-expression phenotype. Finally, the methylation analysis demonstrated a correlation between hypermethylation of the SEMA5B gene and a poor prognosis in KIRC. Increased SEMA5B expression correlated with immune cell infiltration, which can be served as a favorable prognostic factor and a novel diagnostic biomarker for KIRC.
信号素5B（SEMA5B）已被描述为参与癌症的发生和发展。然而，SEMA5B在肾透明细胞癌（KIRC）中的潜在诊断和预后作用及其与肿瘤浸润免疫细胞的相关性尚未见明确报道。通过癌症基因组图谱（TCGA）和基因型组织表达（GTEx）数据库以及癌症细胞系百科全书（CCLE）数据集分析SEMA5B的mRNA水平，并通过GSE53757和GSE40435数据集进行验证。同时，通过临床蛋白质组肿瘤分析联盟（CPTAC）分析SEMA5B的蛋白质水平，并通过人类蛋白质图谱（HPA）进行验证。根据TCGA数据库分析SEMA5B的诊断价值，并通过GSE53757、GSE46699以及GSE11024 + GSE46699数据集进行验证。然后，使用GEPIA2进行生存分析。应用R软件（v3.6.3）研究SEMA5B与免疫检查点以及m6A RNA甲基化调节因子表达之间的相关性。通过TIMER2探索SEMA5B与错配修复蛋白（MMRs）、DNA甲基转移酶（DNMTs）表达以及肿瘤浸润免疫细胞之间的相关性。通过cBioPortal评估SEMA5B的共表达基因，并通过Metascape进行富集分析。使用MEXPRESS和MethSurv在线工具进行甲基化分析。应用基因集富集分析（GSEA）注释SEMA5B的生物学功能。在KIRC中，SEMA5B在mRNA和蛋白质水平均显著上调。进一步分析表明，SEMA5B的mRNA表达与性别、年龄、T分期、病理分期和组织学分级显著相关。高水平的SEMA5B被发现是KIRC的一个良好预后因素和新型诊断生物标志物。SEMA5B的表达与KIRC中免疫细胞的丰度显著相关。此外，SEMA5B的表达与KIRC中MMR基因、DNMTs和m6A调节因子的丰度显著相关。富集分析表明，共表达基因可能参与细胞外基质（ECM）中的交联。GSEA显示，系统性红斑狼疮和NABA细胞外基质调节因子在SEMA5B低表达表型中显著富集。最后，甲基化分析表明SEMA5B基因的高甲基化与KIRC的不良预后相关。SEMA5B表达增加与免疫细胞浸润相关，可作为KIRC的一个良好预后因素和新型诊断生物标志物。
