Evidence map›Paper›PMID 41572218›Full record

ArticleBMC cancer2026

Integrative multi-omics reveal a CD4⁺ T cell-derived six-gene signature linking the immune-stromal ecosystem to prognosis and immunotherapy selection in pancreatic cancer.

Yuxin Liang, Shuoshuo Ma, Xing Chen, Yuhao Su, Deyuan Zhong, Hongtao Yan, Yahui Chen, Ming Wang, Zhengwei Leng, Xiaolun Huang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Yuxin LiangLiver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China.
Shuoshuo MaLiver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China.
Xing ChenState Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, 999078, China.
Yuhao SuLiver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China.
Deyuan ZhongLiver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China.
Hongtao YanLiver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China.
Yahui ChenLiver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China.
Ming WangLiver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China.
Zhengwei LengLiver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China.
Xiaolun HuangLiver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China. huangxiaolun@med.uestc.edu.cn.

Funding

Noncommunicable Chronic Diseases-National Science and Technology Major Project 2024ZD0525500/2024ZD0525506Research Project of Science and Technology Department of Sichuan Province 2024YFHZ0358
6 · The paper itself

Abstract

backgroundPancreatic cancer (PC) exhibits dismal outcomes and an immune-excluded microenvironment that blunts immunotherapy. Robust, immune-anchored biomarkers are needed to stratify risk and inform treatment design.

methodsWe integrated The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) dataset and validated findings in Gene Expression Omnibus (GEO) dataset (GSE57495). Immune infiltration, survival modeling, pathway activity, tumor microenvironment, and immunotherapy responses were analyzed. Single-cell RNA sequencing (GSE212966) informed CD4⁺ T-cell differentially expressed genes (DEGs), pseudotime, and intercellular communication (CellChat). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot in H6C7, CAPAN-1, and PANC-1 cell lines were performed.

resultsAmong 28 immune subsets, CD4⁺ T-cell populations most strongly associated with overall survival (OS). A six-gene signature (KLF3, EZR, SMDT1, JPT1, ISG15, MT1X) derived from 111 CD4⁺ T-cell DEGs successfully stratified OS with time-dependent AUCs ranging from 0.637 to 0.838 across the training and validation cohorts. The high-risk group showed significantly poorer OS, higher stromal scores, broad checkpoint upregulation, and greater immune exclusion (P < 0.05), indicating an immune-stromal ecosystem favoring tolerance. Single-cell RNA sequencing localized model genes to fibroblasts, ductal cells, and CD4⁺ T cells subsets. CellChat revealed globally intensified crosstalk in PC and strengthened CD4⁺ T-cell interactions with myeloid and stromal compartments. Western blot and qRT-PCR results confirmed up-expression of all model gene except SMDT1 in PC cell lines.

conclusionsCD4⁺ T-cell subsets serve as central determinant of the immune landscape and clinical outcome in PC. The CD4⁺ T cell-anchored six-gene signature enables risk stratification, links immune contexture to stromal ecology, and motivates biomarker-guided trials and rational combinations that alleviate immunosuppression while targeting metabolic-stress pathways.

Indexed as

Biomarkers, TumorCD4-Positive T-LymphocytesImmunotherapyPancreatic NeoplasmsTumor MicroenvironmentCell Line, TumorGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMultiomicsPrognosisStromal CellsTranscriptomeBiomarkers, TumorBiomarkerCD4⁺ t cellImmune–stromal ecosystemPancreatic cancerPrognosisTumor immune microenvironment

Identifiers

PMID41572218
PMCPMC12915028

What OpenQuestion holds

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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 OpenQuestion graph.