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

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

doi:10.1016/j.csbj.2022.06.039

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

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

Authors

Ning Wang¹, Lingye Zhu¹, Liangxing Wang¹, Zhifa Shen², Xiaoying Huang¹

Affiliations

¹ Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, PR China.
² 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.

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.

Keywords: 3D, three-dimensional; ACC, adrenocortical carcinoma; AUC, area under the curve; BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; Biomarker; CAF, cancer-associated fibroblasts; CCLE, cancer cell line encyclopedia; CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; DEGs, differentially expressed genes; DFS, disease free survival; DLBC, lymphoid neoplasm diffuse large B-cell lymphoma; DSS, disease specific survival; Diagnosis; ER, endoplasmic reticulum; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; GO, Gene Ontology; GSEA, Gene Set Enrichment Analysis; GTEx, genotype-tissue expression; HNSC, head and neck squamous cell carcinoma; HR, hazard ratio; ICIs, immune checkpoint inhibitors; Immuno-oncology; KEGG, Kyoto encyclopedia of genes and genomes; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LAML, acute myeloid leukemia; LGG, brain lower grade glioma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MDSC, myeloid-derived suppressor cells; MESO, mesothelioma; MSI, microsatellite instability; OS, overall survival; OV, ovarian serous cystadenocarcinoma; PAAD, pancreatic adenocarcinoma; PCPG, pheochromocytoma and paraganglioma; PFS, progression free survival; PPI, protein–protein interaction; PRAD, prostate adenocarcinoma; Pan-cancer; Prognosis; READ, rectum adenocarcinoma; ROC, receiver operating characteristic; SARC, sarcoma; SHCBP1; SHCBP1, Shc SH2-domain binding protein 1; SKCM, skin cutaneous melanoma; STAD, stomach adenocarcinoma; TAM, tumor-associated macrophages; TCGA, the cancer genome atlas; TGCT, testicular germ cell tumors; THCA, thyroid carcinoma; THPA, the human protein atlas; THYM, thymoma; TIME, tumor immune microenvironment; TIMER 2.0, tumor immune estimation resource, version 2; TMB, tumor mutational burden; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma; UVM, uveal melanoma.