Evidence map›Paper›PMID 41916296›Full record

ArticleCell reports. Medicine2026

Robust transcriptomic hallmarks targeting intratumor heterogeneity in intrahepatic cholangiocarcinoma.

Youpei Lin, Lihua Peng, Haichao Zhao, Penghui Lin, Lv Chen, Zunyun Gong, Jian Lin, Dongbing Liu, Xupeng Yang, Xiangze Song and 24 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

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

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

34 authors.

Youpei LinDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Lihua PengState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou 310030, China.
Haichao ZhaoDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Penghui LinBGI Genomics, Shenzhen 518083, China.
Lv ChenDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Zunyun GongCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing 100000, China.
Jian LinZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China.
Dongbing LiuBGI Genomics, Shenzhen 518083, China; Jiangxi Provincial Key Laboratory of Organ Development and Epigenetics, School of Basic Medicine, Jinggangshan University, Ji'an 343009, China.
Xupeng YangDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Xiangze SongState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou 310030, China; School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.
Mao ZhangDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Shuyi JiInstitute for Regenerative Medicine, Medical Innovation Center and State Key Laboratory of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200123, China.
Junhua RaoBGI, Shenzhen 518083, China.
Huijuan LuoBGI Genomics, Shenzhen 518083, China.
Yifei ChengDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Xiaofang ChenState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou 310030, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100000, China.
Guohe SongDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Hao HouState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou 310030, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100000, China.
Dongning RaoDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Tiancheng ZhangDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Weiren LiuDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Shu ZhangDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Gaoyang XuState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou 310030, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100000, China.
Juan ZhangDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Liyun XiaoState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou 310030, China.
Yan LiangBGI Genomics, Shenzhen 518083, China.
Yang LiuState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou 310030, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100000, China.
Yuhan ChenState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou 310030, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100000, China.
Zhirou CuiState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou 310030, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100000, China.
Xiaoying WangDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Jian ZhouDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Qiang GaoDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China; Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433, China. Electronic address: gaoqiang@fudan.edu.cn.
Kui WuState Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou 310030, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100000, China; Jiangxi Provincial Key Laboratory of Organ Development and Epigenetics, School of Basic Medicine, Jinggangshan University, Ji'an 343009, China. Electronic address: wukui@genomics.cn.
Jia FanDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China; Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433, China. Electronic address: fan.jia@zs-hospital.sh.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Intratumor heterogeneity (ITH) undermines transcriptome-based stratification in intrahepatic cholangiocarcinoma (iCCA). Here, we integrate multi-omics data from multi-region, single-region, and single-cell RNA sequencing cohorts to systematically characterize gene expression ITH. We uncover that immune and stromal heterogeneity are primary drivers of ITH, leading to misclassification of a median 27.8% of tumors by existing subtyping systems. To overcome this, we identify a low-intratumor-heterogeneity/high-intertumor-variability (LIHV) gene set and develop an ITH-insensitive classification system defining five subgroups: inflammatory (SI), metabolic (SII), atypical (SIII-1), immune-silent (SIII-2), and neurodegenerative (SIII-3). These subgroups exhibit distinct clinical outcomes, molecular features, immune landscapes, and therapeutic vulnerabilities. GPRC5A and VTCN1 serve as robust immunohistochemical biomarkers for SI and SIII tumors, while serum CEA and CA19-9 identify inflammatory iCCA. Therapeutically, HSP90 inhibition synergizes with anti-PD1 in inflammatory iCCA, whereas combined anti-PD1 and anti-TIM3 suppresses neurodegenerative iCCA. Collectively, our study provides a robust molecular framework and actionable therapeutic strategies for iCCA.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaGenetic HeterogeneityTranscriptomeBiomarkers, TumorGene Expression Regulation, NeoplasticHSP90 Heat-Shock ProteinsHumansTumor MicroenvironmentBiomarkers, TumorHSP90 Heat-Shock ProteinscholangiocarcinomaGPRC5AHSP90 inhibitorimmunotherapyintratumor heterogeneitymolecular classificationmulti-omicsprecision oncologytumor biomarkertumor immune microenvironment

Identifiers

PMID41916296
PMCPMC13130669

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