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鉴定SHCBP1作为一种潜在的生物标志物,涉及多种癌症的诊断、预后及肿瘤免疫微环境。

Identification of SHCBP1 as a potential biomarker involving diagnosis, prognosis, and tumor immune microenvironment across multiple cancers.

作者信息

Wang Ning, Zhu Lingye, Wang Liangxing, Shen Zhifa, Huang Xiaoying

机构信息

Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, PR China.

Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, PR China.

出版信息

Comput Struct Biotechnol J. 2022 Jun 18;20:3106-3119. doi: 10.1016/j.csbj.2022.06.039. eCollection 2022.

Abstract

Shc SH2-domain binding protein 1 (SHCBP1), a protein specific binding to SH2 domain of Src homolog and collagen homolog (Shc), takes part in the regulation of various signal transduction pathways, which has been reported to be associated with tumorigenesis and progression. However, the pathological mechanisms are not completely investigated. Thus, this study aimed to comprehensively elucidate the potential functions of SHCBP1 in multiple cancer types. The comprehensive analyses for SHCBP1 in various tumors, including gene expression, diagnosis, prognosis, immune-related features, genetic alteration, and function enrichment, were conducted based on multiple databases and analysis tools. SHCBP1 was upregulated in most types of cancers. The results of qRT-PCR had confirmed that SHCBP1 mRNA was significantly upregulated in lung adenocarcinoma (LUAD) and liver hepatocellular carcinoma (LIHC) cell lines. Based on the receiver operating characteristic (ROC) and survival analysis, SHCBP1 was considered as a potential diagnostic and prognostic biomarker. Furthermore, SHCBP1 expression was linked with tumor immunity and immunosuppressive microenvironment according to the correlation analysis of SHCBP1 expression with immune cells infiltration, immune checkpoint genes, and immune-related genes (MHC genes, chemokines, and chemokines receptors). Moreover, SHCBP1 expression correlated with tumor mutational burden (TMB), microsatellite instability (MSI), and neoantigens. The feature of SHCBP1 mutational landscape in pan-cancer was identified. Finally, we focused on investigating the clinical significance and the potential biological role of SHCBP1 in LUAD. Our study comprehensively uncovered that SHCBP1 could be identified as an immune-related biomarker for cancer diagnosis and prognosis, and a potential therapeutic target for tumor immunotherapy.

摘要

Shc SH2结构域结合蛋白1(SHCBP1)是一种与Src同源物和胶原蛋白同源物(Shc)的SH2结构域特异性结合的蛋白质,参与多种信号转导途径的调节,据报道其与肿瘤发生和进展有关。然而,其病理机制尚未完全阐明。因此,本研究旨在全面阐明SHCBP1在多种癌症类型中的潜在功能。基于多个数据库和分析工具,对SHCBP1在各种肿瘤中的综合分析,包括基因表达、诊断、预后、免疫相关特征、基因改变和功能富集。SHCBP1在大多数癌症类型中上调。qRT-PCR结果证实,SHCBP1 mRNA在肺腺癌(LUAD)和肝细胞癌(LIHC)细胞系中显著上调。基于受试者工作特征(ROC)和生存分析,SHCBP1被认为是一种潜在的诊断和预后生物标志物。此外,根据SHCBP1表达与免疫细胞浸润、免疫检查点基因和免疫相关基因(MHC基因、趋化因子和趋化因子受体)的相关性分析,SHCBP1表达与肿瘤免疫和免疫抑制微环境相关。此外,SHCBP1表达与肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)和新抗原相关。确定了泛癌中SHCBP1突变图谱的特征。最后,我们专注于研究SHCBP1在LUAD中的临床意义和潜在生物学作用。我们的研究全面揭示,SHCBP1可被鉴定为癌症诊断和预后的免疫相关生物标志物,以及肿瘤免疫治疗的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f8/9233189/300387adbba5/ga1.jpg

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