Research Paper Advance Articles

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

Fei Jiang1, *,#, , Yanlong Shi2, *,#, , Yue Wang3, *,#, , Chang Ge1, *,#, , Jun Zhu4, *,#, , Hanlu Fang5, , Yu Zhang6, , Yixiao Zhang7, , Haokun Jian8, , Tong Lei9, , Sheng Lan10, , Liyu Cao3, &, , Hongzhu Yu1, , Debao Fang11,12, ,

  • 1 Department of General Surgery, Fuyang Hospital of Anhui Medical University, Fuyang, Anhui, China
  • 2 Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
  • 3 Department of Pathology, Anhui Medical University, Hefei, Anhui, China
  • 4 Department of Oncology, Fuyang Hospital of Anhui Medical University, Fuyang, Anhui, China
  • 5 School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei, China
  • 6 The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
  • 7 The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
  • 8 School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China
  • 9 The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
  • 10 The Second Clinical College Clinical Medicine, Guangzhou Medical University, Guangzhou, Guangdong, China
  • 11 School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
  • 12 CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
* Equal contribution
# Share first authorship

Received: November 28, 2022       Accepted: March 1, 2023       Published: March 14, 2023      

https://doi.org/10.18632/aging.204591
How to Cite

Copyright: © 2023 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

SHC: Src homolog and collagen homolog; SHCBP1: SHC srchomology 2 domain-binding protein 1; TCGA: The Cancer Genome Atlas; GTEx: Genotype-Tissue Expression; TMB: tumor mutational burden; MSI: microsatellite instability; TIMER2: Tumor Immune Estimation Resource; GEPIA: Gene Expression Profling Interactive Analysis; UALCAN: The University of Alabama at Birmingham Cancer data analysis Portal; CPTAC: clinical proteomic tumor analysis consortium; OS: overall survival; DFS: disease-free survival; FP: first progression; DSS: disease-specific survival; PPS: post-progression survival; PFS: progression-free survival; RFS: relapse-free survival; DMFS: distant metastasis-free survival; TIDE: Tumor Immune Dysfunction and Exclusion; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; HCC: hepatoma carcinoma cell; GC: gastric cancer; CRC: colorectal cancer; RT-qPCR: Quantitative real-time polymerase chain reaction; STRING: Search Tool for the Retrieval of Interaction Gene/Proteins; ICI: immune checkpoint inhibitors.