A pan-cancer analysis uncovering the function of CRHBP in tumor immunity, prognosis and drug response: especially its function in LIHC

Sep 21, 2026

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Corticotropin-releasing hormone-binding protein (CRHBP) is investigated for its roles in tumor immunity, survival prognosis, immune checkpoint signals, tumor mutation burden, microsatellite instability, mismatch repair, DNA methylation, tumor microenvironment features, and drug responsiveness across diverse cancers. Analyses using TCGA, GEO and multiple expression and protein databases link low CRHBP levels with worse prognostic outcomes and immunological associations. Experimental assays in liver hepatocellular carcinoma (LIHC) support a tumor-suppressor function through cell and molecular measurements and CRHBP-centered signaling.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Overview

Pan-cancer database analysis

Association with prognosis and biomarkers

LIHC experimental validation

Biological background of CRHBP

Reported links to other cancers

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN A pan‑cancer analysis uncovering the function ofCRHBP in tumor immunity, prognosis and drug response: especially its function in LIHC Bangjie Chen1,10, Sanwei Chen2,10, Xinyi Wang3,10, Jianlin Zhang4,10, Hanying Wang5, Jiajin Li6, Ziyu Zhang7, Feng Yu8* & Weihao Kong4,9* Corticotropin‑releasing hormone‑binding protein (CRHBP) is involved in many physiological processes. However, it is still unclear what role CRHBP has in tumor immunity and prognosis prediction. Using databases such as the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Tumor Protein Database, Timer Database, and Gene Expression Profiling Interactive Analysis (GEPIA), we evaluated the potential role ofCRHBP in diverse cancers. Further research looked into the relationships between CRHBP and tumor survival prognosis, immune infiltration, immune checkpoint (ICP) indicators, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), DNA methylation, tumor microenvironment (TME), and drug responsiveness. The anticancer effect ofCRHBP in liver hepatocellular carcinoma (LIHC) was shown by Western blotting, EdU staining, JC‑1 staining, transwell test, and wound healing assays. CRHBP expression is significantly low in the majority of tumor types and is associated with survival prognosis, ICP markers, TMB, and microsatellite instability (MSI). The expression ofCRHBP was found to be substantially related to the quantity of six immune cell types, as well as the interstitial and immunological scores, showing that CRHBP has a substantial impact in the TME. We also noticed a link between the IC50 of a number of anticancer medicines and the degree of CRHBP expression. CRHBP‑related signaling pathways were discovered using functional enrichment. Cox regression analysis showed that CRHBP expression was an independent prognostic factor for LIHC. CRHBP has a tumor suppressor function in LIHC, according to cell and molecular biology trials. CRHBP has a significant impact on tumor immunity, treatment, and prognosis, and has the potential as a cancer treatment target and prognostic indicator. CRHBP, a 37 kDa secreted glycoprotein, was found in human plasma as a molecule that interacted with corticotropin-releasing hormone (CRH) radioimmunoassays1. In all vertebrates, CRHBP possesses a highly folded tertiary structure that maintains 10 cysteine residues in 5 consecutive disulfide linkages2,3. As a member of the CRH family, CRHBP differs structurally from CRHR (CRH receptor) and has higher affinity for binding CRHand UCN1 (urocortin I) than CRHR, but variable or less affinity for UCN2 (urocortin II) and UCN3 (urocortin III)4,5. The CRH and CRHR physiological responses are modulated by CRHBP, which is associated with the hypothalamic–pituitary–adrenal (HPA) axis2,6,7. It can control a range of physiological responses, including 1Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China. 2Department of General Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, China. 3Department of Radiation Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China. 4Department of Emergency Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China. 5Department of Operation Theater, First Affiliated Hospital of Anhui Medical University, Hefei, China. 6The Second Clinical Medical College of Anhui Medical University, Hefei, China. 7The First Clinical Medical College of Anhui Medical University, Hefei, China. 8Department of Emergency Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China. 9Gastrointestinal Surgery Department, West China Hospital of Sichuan University, Chengdu, China. 10These authors contributed equally: Bangjie Chen, Sanwei Chen, Xinyi Wang and Jianlin Zhang. *email: yufeng1110@ [sina.com](sina.com); [kongwh3@mail2.sysu.edu.cn](ko

FAQs

CRHBP在肿瘤免疫和预后预测中被重点研究了哪些方面？

研究围绕免疫浸润、免疫检查点指标、肿瘤突变负担（TMB）、微卫星不稳定（MSI）、错配修复（MMR）、DNA甲基化、肿瘤微环境（TME）以及药物响应展开。

CRHBP的表达与生存预后和免疫相关指标有什么关系？

在多数肿瘤类型中CRHBP表达显著偏低，并与生存预后、免疫检查点标志物、TMB以及MSI相关；同时与多类免疫细胞数量及免疫和间质相关评分存在联系。

LIHC中如何验证CRHBP的抗肿瘤作用？

通过Western blotting、EdU、JC-1、Transwell迁移/侵袭及划痕愈合等细胞与分子实验评估抗癌效应，结果支持CRHBP在LIHC中具有肿瘤抑制功能。

Sep 21, 2026

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