Evidence map›Paper›PMID 41073999›Full record

ArticleCancer cell international2025

EDC4 enhances multi-drug chemosensitivity in pancreatic cancer via GR50-based profiling.

Cheng Qin, Tianyu Li, Bangbo Zhao, Zeru Li, Yutong Zhao, Xiangyu Zhang, Yiping Xie, Yutong Yan, Jiashu Han, Qianqian Shao and 2 more

Abstract read
In one paragraph

Article in Cancer cell international, 2025. 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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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

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Cheng Qin *Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Tianyu Li *Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Bangbo Zhao *Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Zeru LiDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yutong ZhaoDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Xiangyu ZhangDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yiping XieDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yutong YanDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Jiashu HanDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Qianqian ShaoDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Chen LinDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. linchen0818@sina.com.
Weibin WangDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. wwb_xh@163.com.

Funding

Beijing Natural Science Foundation 7232127CAMS Innovation Fund for Medical Sciences 2021-I2M-1-002National High Level Hospital Clinical Research Funding No. 2022-PUMCH-D-001, No. 2022-PUMCH-B-004National Natural Science Foundation of China 82173074
6 · The paper itself

Abstract

backgroundPancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, with drug resistance significantly impeding effective chemotherapy. The clinical importance of key genes in PDAC chemoresistance remains unclear.

methodsCytotoxicity assays were conducted on eight PDAC cell lines treated with gemcitabine, albumin paclitaxel, irinotecan, 5-FU, and cis-platinum. Based on GR50 values, cell lines were categorized as chemosensitive (CS) or chemoresistant (CR). RNA-seq data from the Cancer Cell Line Encyclopedia were analyzed for differential gene expression. Various statistical methods, including univariate Cox, LASSO, random forest, and multivariate Cox regression, were employed to construct a risk signature. This model's effectiveness was validated using time-dependent ROC curves and Kaplan-Meier survival analysis in TCGA and GSE57495 + GSE28735 combined datasets. Downstream molecules of core genes were explored, and the core gene's function was validated through in vivo and in vitro experiments.

resultsDrug resistance profiles were established based on GR50 values. EDC4 and USP20 were identified as key genes in the risk signature. qRT-PCR validated core gene expressions in PDAC cell lines. EDC4 was selected for further analysis due to its highest correlation coefficient in the multivariate Cox regression model. EDC4 knockdown increased proliferation and chemoresistance in MIA PaCa-2 cells, while overexpression inhibited these traits in AsPC-1 cells. MATN3 and SGCE were identified as downstream targets of EDC4. Immunohistochemistry of tissue microarrays confirmed that low EDC4 levels were associated with poor prognosis in PDAC, highlighting its potential as a therapeutic target.

conclusionPDAC cell lines exhibit distinct chemoresistance capabilities. EDC4 and its downstream targets MATN3 and SGCE play significant roles in PDAC multidrug chemoresistance, providing novel insights for treatment.

Identifiers

PMID41073999
PMCPMC12512939

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