SHCBP1 在泛癌中的预后和免疫景观特征：生物标志物和治疗靶点的新见解。

Characterization of SHCBP1 to prognosis and immunological landscape in pan-cancer: novel insights to biomarker and therapeutic targets.

机构信息

Department of General Surgery, Fuyang Hospital of Anhui Medical University, Fuyang, Anhui, China.

Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

Aging (Albany NY). 2023 Mar 14;15(6):2066-2081. doi: 10.18632/aging.204591.

DOI:10.18632/aging.204591

PMID:36920183

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10085602/

Abstract

BACKGROUND

Previous studies have revealed the significant roles of SHC SH2 domain-binding protein 1 (SHCBP1) in occurrence and progression of cancers, but there is no pan-cancer analysis of SHCBP1.

METHODS

In this study, we explored the potential carcinogenic role of SHCBP1 across 33 tumors from the TCGA and GTEx databases. We investigated SHCBP1 expression, prognosis, genetic alterations, tumor mutational burden (TMB) score, microsatellite instability (MSI) and tumor microenvironment from TIMER2, GEPIA2, UALCAN and cBioPortal databases. Moreover, the cellular functions and potential mechanisms were evaluated by GO and KEGG analysis. Besides, the mRNA expression of SHCBP1 was examined using qRT-PCR assay in gastrointestinal cancers.

RESULTS

SHCBP1 was significantly upregulated in various cancers, and apparent relationship existed between SHCBP1 and survival prognosis in patients. The TMB, MSI, and tumor microenvironment analysis indicated that SHCBP1 was closely related to immune checkpoints, immune targets, as well as CD4+ naive T cell, CD8+ T cell, and neutrophil. Moreover, the cellular functions of SHCBP1 were mainly in regulating cell cycle motor protein activity. In addition, we validated that SHCBP1 mRNA expression was over-expressed in gastrointestinal cancers.

CONCLUSIONS

This study was the first to systematically determine the prognostic value of SHCBP1, providing a forward-looking perspective on immunotherapy and cellular processes in pan-cancer.

摘要

背景

先前的研究表明 SHC SH2 域结合蛋白 1（SHCBP1）在癌症的发生和发展中具有重要作用，但尚无针对 SHCBP1 的泛癌分析。

方法

在这项研究中，我们从 TCGA 和 GTEx 数据库中研究了 33 种肿瘤中 SHCBP1 的潜在致癌作用。我们从 TIMER2、GEPIA2、UALCAN 和 cBioPortal 数据库中研究了 SHCBP1 的表达、预后、遗传改变、肿瘤突变负担（TMB）评分、微卫星不稳定性（MSI）和肿瘤微环境。此外，通过 GO 和 KEGG 分析评估了细胞功能和潜在机制。此外，使用 qRT-PCR 检测胃肠道癌症中 SHCBP1 的 mRNA 表达。

结果

SHCBP1 在各种癌症中显著上调，并且在患者中存在明显的 SHCBP1 与生存预后的关系。TMB、MSI 和肿瘤微环境分析表明，SHCBP1 与免疫检查点、免疫靶标以及 CD4+naive T 细胞、CD8+T 细胞和中性粒细胞密切相关。此外，SHCBP1 的细胞功能主要在于调节细胞周期马达蛋白活性。此外，我们验证了胃肠道癌症中 SHCBP1 的 mRNA 表达呈过表达。