Evidence map›Paper›PMID 42001193›Full record

ArticleBiology direct2026

The B7 family subgroup reflects tumor cell heterogeneity and patient post-operative prognosis in gallbladder cancer.

Chuhan Ma, Huixin Hu, Yang Li, Chongli Zhong, YunHao Dong, Zhanhao Chang, Shuo Xu, Yuyang Zhang, Hangqi Hu, Chao Lv and 1 more

Erratum issuedAbstract read
In one paragraph

Article in Biology direct, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Chuhan Ma *Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, P. R. China.
Huixin Hu *Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, P. R. China.
Yang Li *Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, P. R. China.
Chongli ZhongDepartment of Interventional Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
YunHao DongDepartment of Computer Science and Software Engineering, Shenzhen University, Shenzhen, China.
Zhanhao ChangDepartment of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, P. R. China.
Shuo XuDepartment of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, P. R. China.
Yuyang ZhangDepartment of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, P. R. China.
Hangqi HuDepartment of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Chao LvDepartment of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, P. R. China. clu@cmu.edu.cn.
Yu TianDepartment of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, P. R. China. yu.tian@cmu.edu.cn.

Funding

Department of Science and Technology of Liaoning Province 2023JH2/20200128National Natural Science Foundation of China 81974377
6 · The paper itself

Abstract

purposeTo elucidate the biological heterogeneity of gallbladder cancer (GBC) cells and refine post-operative risk stratification by investigating the expression and downstream signaling of the B7-family immune checkpoint molecules CD276 (B7-H3), VTCN1 (B7-H4), and HHLA2 (B7-H7) at single-cell resolution.

methodsSingle-cell RNA sequencing (scRNA-seq) data from seven primary tumors delineated five epithelial subgroups via non-negative matrix factorization (NMF). The functional association between HHLA2 and RAC1/CDC42-PAK1-Cofilin signaling was validated by lentiviral manipulation, pharmacologic inhibition, and subcutaneous xenografts. A total of 188 surgically treated GBC patients were enrolled for survival modeling. Seven machine-learning survival algorithms were trained on five variables (CD276, VTCN1, HHLA2 expression, tumor size, and differentiation) and compared by C-index, ROC-AUC, and calibration curves.

resultsCD276 + and VTCN1 + epithelial cells displayed pro-proliferative profiles, whereas HHLA2 + cells exhibited high EMT and migration signatures. HHLA2 overexpression led to increased RAC1/CDC42-PAK1-Cofilin signaling activity, enhanced proliferation, invasion, and EMT in vitro, and accelerated tumor growth in vivo. These effects were reversed by RAC1, CDC42, or PAK1 inhibitors, as well as by CFL1 knockdown. NMF classified tumor epithelial cells into five functionally distinct subgroups. A gradient-boosting machine (GBM) model integrating expression of the three B7 molecules with tumor size and differentiation achieved superior discrimination and accurate calibration on both the training and validation sets.

conclusionB7-family expression delineates biologically distinct GBC subpopulations; HHLA2 promotes EMT via RAC1/CDC42-PAK1-Cofilin signaling. The GBM model incorporating CD276, VTCN1, and HHLA2 expression with tumor size and differentiation demonstrates potential for enhanced post-operative risk stratification, offering promising candidates for biomarker development and targeted therapeutic interventions.

Indexed as

Gallbladder NeoplasmsAnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMaleMicePrognosisSignal TransductionCD276Gallbladder cancerHHLA2PrognosisVTCN1

Identifiers

PMID42001193
PMCPMC13224545

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

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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 Socratic graph.