Evidence map›Paper›PMID 42708082›Full record

ArticleTheranostics2026

Membrane and soluble VTCN1 (B7H4) converge on Src signaling to mediate gemcitabine resistance in intrahepatic cholangiocarcinoma.

Yi-Ru Pan, Sheng-Hsuan Lin, Yu-Chan Chang, Shih-Ming Jung, Chiao-En Wu, Wen-Kuan Huang, Chun-Nan Yeh

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Article in Theranostics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Yi-Ru PanDepartment of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, Taoyuan 333, Taiwan.
Sheng-Hsuan LinDepartment of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, Taoyuan 333, Taiwan.
Yu-Chan ChangDepartment of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
Shih-Ming JungDepartment of Pathology, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan.
Chiao-En WuDivision of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
Wen-Kuan HuangDivision of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
Chun-Nan YehDepartment of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, Taoyuan 333, Taiwan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rationale: A combination of gemcitabine (GEM)-based chemotherapy and an immune checkpoint inhibitor is the standard treatment for patients with advanced intrahepatic cholangiocarcinoma (iCCA). However, 70% of patients develop progressive disease following GEM treatment, highlighting the urgent need for therapeutic strategies targeting GEM-resistant (GR) disease. Methods: We established GR iCCA sublines and identified 9 upregulated genes by RNA-sequencing and cDNA microarray. Among the 9 genes, we demonstrated that VTCN1 expression improved GR. The enhanced effect of VTCN1 on GR was validated in a spontaneous rat iCCA model, a xenograft mouse model, an orthotopic mouse model, and iCCA specimens. A phospho-kinase array was used to identify the downstream effector of membrane and soluble VTCN1 (sVTCN1). Results: VTCN1 expression was significantly elevated in GEM non-responders and independently predicted poor progression-free survival (HR = 2.038, P = 0.035). Plasma sVTCN1 levels correlated with tumor VTCN1 expression ( Conclusions: Membrane and soluble VTCN1 drive GR through dual pathways converging on Src activation. VTCN1 represents both a prognostic biomarker and therapeutic target, with Src inhibition providing a rational strategy to overcome chemotherapy resistance in iCCA.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaDeoxycytidineDrug Resistance, Neoplasmsrc-Family KinasesV-Set Domain-Containing T-Cell Activation Inhibitor 1AnimalsAntimetabolites, AntineoplasticCell Line, TumorGemcitabineHumansMaleMiceRatsSignal TransductionXenograft Model Antitumor AssaysAntimetabolites, AntineoplasticDeoxycytidineGemcitabinesrc-Family KinasesV-Set Domain-Containing T-Cell Activation Inhibitor 1VTCN1 protein, humanB7H4gemcitabine resistanceintrahepatic cholangiocarcinomasoluble VTCN1Src.

Identifiers

PMID42708082
PMCPMC13549373

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.