Chen Jianlin, Gao Gan, Li Limin, Ding Junping, Chen Xianhua, Lei Jianfei, Long Haihua, Wu Lihua, Long Xin, He Lian, Shen Yongqi, Yang Jinzhong, Lu Yonggang, Sun Yifan
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.
Departments of Clinical Laboratory of Liuzhou Maternity and Child Healthcare Hospital, Liuzhou, China.
Front Genet. 2022 May 2;13:817118. doi: 10.3389/fgene.2022.817118. eCollection 2022.
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. 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." SHC1 was ubiquitously highly expressed and closely associated with worse prognosis of multiple major cancer types (all < 0.05). Further, SHC1 gene mutations were strongly linked to poor OS and DFS in SKCM (all < 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 < 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. 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.
近期研究突显了SHC衔接蛋白1（SHC1）在癌症起始、发展和进展中的致癌作用。然而，其在多种肿瘤中的异常表达、诊断和预后价值仍不清楚。使用GTEx数据库、TCGA数据库、Oncomine和CPTAC数据库分析SHC1表达谱。使用GEPIA2、Kaplan-Meier Plotter、UALCAN和PrognoScan进行生存分析。用R软件中的“pROC”软件包计算SHC1的诊断价值。使用cBioPortal分析SHC1的基因改变和突变。利用TIMER2评估TCGA队列中SHC1表达与肿瘤浸润免疫细胞之间的相关性。使用R软件包“clusterProfiler”进行SHC1的富集分析。SHC1在多种主要癌症类型中普遍高表达，且与较差的预后密切相关（均P<0.05）。此外，SHC1基因突变与皮肤黑色素瘤（SKCM）中较差的总生存期（OS）和无病生存期（DFS）密切相关（均P<0.05）。在透明细胞肾细胞癌中观察到SHC1在S139位点的磷酸化水平增强。此外，结果显示SHC1表达与多种癌症中的肿瘤突变负荷（TMB）、错配修复（MMR）、微卫星高度不稳定（MSI）、肿瘤相关巨噬细胞（TAM）、DNA甲基化、N6-甲基腺苷（m6A）RNA甲基化、肿瘤相关免疫浸润和免疫检查点密切相关（均P<0.05）。此外，受试者工作特征（ROC）分析结果表明，SHC1对肾嫌色细胞癌（KICH）（曲线下面积[AUC]=0.92）、肝细胞癌（LIHC）（AUC=0.95）和胰腺癌（PAAD）（AUC=0.95）具有较强的诊断能力。最后，富集分析表明，SHC1可能潜在参与癌症代谢和蛋白质磷酸化相关功能中众多信号通路的调控。这些发现突显了SHC1在肿瘤免疫微环境中起重要作用，且已确定SHC1在多种癌症中具有预后和诊断价值。因此，SHC1是癌症免疫治疗的潜在靶点以及有效的预后和诊断生物标志物。
