Evidence map›Paper›PMID 41937206›Full record

ArticleExperimental hematology & oncology2026

Multi-omics analysis of patient-derived organoids reveals that E3 ligase COP1 promotes liver metastasis and oxaliplatin resistance in colorectal cancer through LUZP1 degradation and MYL9 phosphorylation.

Ruijia Zhang, Wenqin Luo, Qikai Zhou, Dongguo Liang, Yuankai Hao, Fan Chen, Yulin Qiu, Yixian Cao, Zezhi Shan, Yu Zhang and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental hematology & oncology, 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
–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

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

16 authors.

Ruijia Zhang *Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Wenqin Luo *Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Qikai Zhou *School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
Dongguo Liang *Shanghai Institute of Hematology, National Research Center for Translational Medicine, State Key Laboratory of Medical Genomics, Ruijin Hospital , Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuankai HaoSchool of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
Fan ChenDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Yulin QiuDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Yixian CaoSchool of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
Zezhi ShanDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Yu ZhangDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Qingguo LiDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Sanjun CaiDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Dakui LuoDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. dkluo17@fudan.edu.cn.
Shaobo MoDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. shaobom@shca.org.cn.
Bin MaShanghai Key Laboratory for Cancer System Regulation and Clinical Translation, Shanghai Jiading District Central Hospital, Shanghai, China. bin.ma@outlook.com.
Xinxiang LiDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. xinxiangli@fudan.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Colorectal cancer liver metastasis (CRLM) and chemotherapy resistance remain major clinical challenges, with the underlying molecular mechanisms yet to be fully elucidated. In this study, based on analyses of five initial clinical cohorts from FUSCC, the E3 ubiquitin ligase COP1 was identified as a critical driver of CRLM and resistance to oxaliplatin-based chemotherapy. Using an organoid biobank derived from paired primary colorectal tumors and liver metastases, integrated multi-omics analyses (WES, bulk RNA-seq, scRNA-seq) of patient-derived organoids (PDOs) from CRLM revealed significantly elevated COP1 expression in liver metastases compared to primary tumors. High COP1 levels were associated with poor prognosis, increased liver metastatic burden, and resistance to oxaliplatin-based chemotherapy. In vitro and in vivo functional experiments demonstrated that COP1 facilitates CRLM progression by ubiquitinating and degrading LUZP1, thereby releasing DAPK3 from LUZP1-mediated suppression. This process leads to enhanced MYL9 phosphorylation and activation of epithelial-mesenchymal transition (EMT) as well as the JAK2-STAT3-CCND2 signaling axis-pathways crucial for liver metastasis and resistance to oxaliplatin-based chemotherapy. These findings establish the COP1-LUZP1-MYL9 axis as a therapeutic target for CRLM and oxaliplatin-based chemoresistance. Clinically, COP1 expression profiling in PDOs from postoperative specimens enables a precision strategy for managing oxaliplatin-based chemoresistance, especially in the context of FOLFOX.

Identifiers

PMID41937206
PMCPMC13094177

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.