Pan-Cancer Study of SHC-Adaptor Protein 1 (SHC1) as a Diagnostic, Prognostic and Immunological Biomarker in Human Cancer

Jianlin Chen; Gan Gao; Limin Li; Junping Ding; Xianhua Chen; Jianfei Lei; Haihua Long; Lihua Wu; Xin Long; Lian He; Yongqi Shen; Jinzhong Yang; Yonggang Lu; Yifan Sun

doi:10.3389/fgene.2022.817118

Pan-Cancer Study of SHC-Adaptor Protein 1 (SHC1) as a Diagnostic, Prognostic and Immunological Biomarker in Human Cancer

Front Genet. 2022 May 2:13:817118. doi: 10.3389/fgene.2022.817118. eCollection 2022.

Authors

Jianlin Chen¹, Gan Gao², Limin Li³, Junping Ding¹, Xianhua Chen¹, Jianfei Lei⁴, Haihua Long¹, Lihua Wu¹, Xin Long¹, Lian He⁴, Yongqi Shen¹, Jinzhong Yang⁴, Yonggang Lu¹, Yifan Sun¹

Affiliations

¹ Departments of Clinical Laboratory, Key Laboratory of medical molecular diagnostics of Liuzhou, Key Laboratory for nucleic acid molecular diagnosis and application of Guangxi health and wellness Commission, Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, China.
² Departments of Clinical Laboratory of Liuzhou Maternity and Child Healthcare Hospital, Liuzhou, China.
³ Departments of Clinical Laboratory of Liuzhou People's Hospital, Liuzhou, China.
⁴ People's Hospital of Rong'an County, Liuzhou, China.

Abstract

Background: Recent studies highlight the carcinogenesis role of SHC-adaptor protein 1 (SHC1) in cancer initiation, development, and progression. However, its aberrant expression, diagnostic and prognostic value remain unknown in a variety of tumors. Methods: The SHC1 expression profiles were analyzed using GTEx database, TCGA database, Oncomine and CPTAC database. The survival analysis was conducted using GEPIA2, Kaplan-Meier Plotter, UALCAN, and PrognoScan. The diagnostic values of SHC1 were calculated with the "pROC" package in R software. The genetic alteration of SHC1 and mutations were analyzed using cBioPortal. TIMER2 was employed to estimate the correlations between SHC1 expression and tumor-infiltrating immune cells in the TCGA cohort. Enrichment analysis of SHC1 was conducted using the R package "clusterProfiler." Results: SHC1 was ubiquitously highly expressed and closely associated with worse prognosis of multiple major cancer types (all p < 0.05). Further, SHC1 gene mutations were strongly linked to poor OS and DFS in SKCM (all p < 0.05). An enhanced phosphorylation level of SHC1 at the S139 site was observed in clear cell RCC. Additionally, the results revealed SHC1 expression was strongly linked to TMB, MMRs, MSI, TAMs, DNA methylation, m6A RNA methylation, tumor-associated immune infiltration, and immune checkpoints in multiple cancers (all p < 0.05). In addition, the results of the ROC analysis indicated the SHC1 exhibited strong diagnostic capability for KICH (AUC = 0.92), LIHC (AUC = 0.95), and PAAD (AUC = 0.95). Finally, enrichment analysis indicated that SHC1 may potentially involve in the regulation of numerous signaling pathways in cancer metabolism and protein phosphorylation-related functions. Conclusions: These findings highlight that SHC1 plays an important role in the tumor immune microenvironment, and SHC1 has been identified to have prognostic and diagnostic value in multiple cancers. Thus, SHC1 is a potential target for cancer immunotherapy and effective prognostic and diagnostic biomarker.

Keywords: SHC1; TCGA; biomarker; pan-cancer; prognosis; tumor immunity.