Prognostic and Diagnostic Values of Semaphorin 5B and Its Correlation With Tumor-Infiltrating Immune Cells in Kidney Renal Clear-Cell Carcinoma

Junping Ding; Shubin Zhao; Xianhua Chen; Changjun Luo; Jinjian Peng; Jiantan Zhu; Yongqi Shen; Zhou Luo; Jianlin Chen

doi:10.3389/fgene.2022.835355

Prognostic and Diagnostic Values of Semaphorin 5B and Its Correlation With Tumor-Infiltrating Immune Cells in Kidney Renal Clear-Cell Carcinoma

Front Genet. 2022 Apr 11:13:835355. doi: 10.3389/fgene.2022.835355. eCollection 2022.

Authors

Junping Ding¹, Shubin Zhao¹, Xianhua Chen², Changjun Luo³, Jinjian Peng¹, Jiantan Zhu¹, Yongqi Shen⁴, Zhou Luo⁵, Jianlin Chen²

Affiliations

¹ Departments of Urology of Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, China.
² 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.
³ Departments of Cardiology of Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, China.
⁴ Departments of Oncology of Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, China.
⁵ Departments of Infectious Diseases of Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, China.

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: Increased SEMA5B expression correlated with immune cell infiltration, which can be served as a favorable prognostic factor and a novel diagnostic biomarker for KIRC.

Keywords: KIRC; biomarker; diagnostic; prognosis; sema5b.