Identification of NOTCH2 as a prognostic marker for cholangiocarcinoma

Sep 30, 2026

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Cholangiocarcinoma (CCA) is a rare but highly lethal hepatobiliary malignancy, where early and accurate diagnosis remains difficult and most patients lack clear predisposing factors. This study integrates bioinformatics, survival analyses, immunohistochemistry, and drug-sensitivity screening to uncover molecular drivers within the tumor microenvironment. JAG1-NOTCH signaling is implicated in CCA pathogenesis, and higher NOTCH2 expression marks worse outcomes.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

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Abstract

1 Introduction

Tumor microenvironment and single-cell RNA sequencing

Sun et al. Discover Oncology (2026) 17:34 [https://doi.org/10.1007/s12672-025-04217-0](https://doi.org/10.1007/s12672-025-04217-0) Discover Oncology RESEARCH Open Access Identification of NOTCH2 as a prognostic marker for cholangiocarcinoma Fengxiao Sun 1, Meina Li2, Kang Fu 1, Junzhe Su 1, Lin Sun3, Yuan Ma3 and Xiao Hu 1* *Correspondence: Xiao Hu [huxiao202@163.com](huxiao202@163.com)[ ](huxiao202@163.com)1Department of Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China 2Department of Urology, Qingdao Municipal Hospital, Qingdao, China 3Department of ICU, The Affiliated Hospital of Qingdao University, Qingdao, China Abstract Background Cholangiocarcinoma (CCA) is a rare malignancy originating from the hepatobiliary epithelium, accounting for 3–5% of all gastrointestinal cancers worldwide. CCA is notoriously difficult to diagnose and is associated with a high mortality rate. While most cases lack identifiable predisposing factors, emerging evidence suggests that molecular therapies targeting fibroblast growth factor receptor and isocitrate dehydrogenase show promise for specific CCA patients. Methods This study employed a series of comprehensive bioinformatics analyses, survival analyses, immunohistochemistry, and drug sensitivity screening. Results We decoded the dynamic changes in cell populations between cholangiocarcinoma and paired healthy tissues, revealing that JAG1-NOTCH signaling significantly contributes to CCA pathogenesis. Higher NOTCH2 expression was correlated with poor prognosis and validated as a proliferative promoter in cell lines. Additionally, we identified four potential drugs targeting NOTCH2 . Conclusions These findings provide new insights into the molecular basis of NOTCH2-mediated promotion of tumor activity and suggest NOTCH2 as a potential therapeutic target for CCA treatment. Keywords Cholangiocarcinoma, scRNA-seq, Tumor microenvironment, NOTCH2, Prognostic marker 1 Introduction Cholangiocarcinoma (CCA) is a highly aggressive malignancy arising from the epithelial cells lining the biliary tract [1]. CCA is classified into three main subtypes based on tumor location: intrahepatic CCA (iCCA), perihilar CCA (pCCA), and distal CCA (dCCA) [2]. Risk factors include primary sclerosing cholangitis, biliary tract infections, hepatolithiasis, and exposure to environmental toxins [3]. Despite advances in diagnostic techniques, CCA is often diagnosed at advanced stages, leading to limited treatment options and poor prognosis [4]. Therefore, a deeper understanding of the molecular mechanisms underlying CCA is crucial for developing effective treatment strategies. The tumor microenvironment (TME) is a complex ecosystem essential for tumor cell survival and development [5]. Evidence suggests that the TME plays a critical role in © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by-nc-nd/4.0/. Sun et al. Discover Oncology (2026) 17:34 Page 2 of 14 tumor

FAQs

Why is cholangiocarcinoma difficult to diagnose and often lethal?

CCA is hard to diagnose and is associated with high mortality, with many cases presenting limited treatment options at advanced stages.

What approach did the study use to evaluate NOTCH2 in cholangiocarcinoma?

The study combined comprehensive bioinformatics analyses, survival analysis, immunohistochemistry, and drug sensitivity screening.

How is NOTCH2 related to prognosis and tumor activity in this research?

Higher NOTCH2 expression correlated with poor prognosis and was validated as a proliferative promoter in cell lines, supporting NOTCH2 as a potential therapeutic target.

Sep 30, 2026

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