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Membraneless organelles-based integrative analysis constructs an immune-related prognostic signature and identifies NRG1 as a novel methylation biomarker in colorectal cancer
by
Cheng, Jingsong
, Luo, Siqi
, Liu, Guodong
, Chen, Weilong
, Zhu, Xinyi
, Yin, Qingyao
, Chen, Xue
, Wang, Ningxi
, Zhang, Chengxi
, Luo, Rugang
, Zheng, Ziheng
, Wan, Yuanyuan
, Chen, Nanting
in
Algorithms
/ Biomarkers
/ Biomarkers, Tumor - genetics
/ Cell Line, Tumor
/ Chemotherapy
/ Clinical outcomes
/ Colorectal cancer
/ Colorectal carcinoma
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - immunology
/ Colorectal Neoplasms - metabolism
/ Colorectal Neoplasms - mortality
/ Colorectal Neoplasms - pathology
/ Datasets
/ DNA Methylation
/ Down-regulation
/ Ecotypes
/ Female
/ Gene expression
/ Gene Expression Profiling
/ Gene Expression Regulation, Neoplastic
/ Growth factors
/ Humans
/ Immunotherapy
/ liquid-liquid phase separation
/ Male
/ Medical prognosis
/ membraneless organelle
/ methylation
/ Microenvironments
/ Neuregulin-1 - genetics
/ Neuregulin-1 - metabolism
/ Nrg1
/ Organelles
/ Pathogenesis
/ Patients
/ Principal components analysis
/ Prognosis
/ Promoter Regions, Genetic
/ Proteins
/ Survival analysis
/ Transcriptome
/ Transcriptomics
/ Tumor Microenvironment - immunology
/ Tumorigenesis
2025
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Membraneless organelles-based integrative analysis constructs an immune-related prognostic signature and identifies NRG1 as a novel methylation biomarker in colorectal cancer
by
Cheng, Jingsong
, Luo, Siqi
, Liu, Guodong
, Chen, Weilong
, Zhu, Xinyi
, Yin, Qingyao
, Chen, Xue
, Wang, Ningxi
, Zhang, Chengxi
, Luo, Rugang
, Zheng, Ziheng
, Wan, Yuanyuan
, Chen, Nanting
in
Algorithms
/ Biomarkers
/ Biomarkers, Tumor - genetics
/ Cell Line, Tumor
/ Chemotherapy
/ Clinical outcomes
/ Colorectal cancer
/ Colorectal carcinoma
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - immunology
/ Colorectal Neoplasms - metabolism
/ Colorectal Neoplasms - mortality
/ Colorectal Neoplasms - pathology
/ Datasets
/ DNA Methylation
/ Down-regulation
/ Ecotypes
/ Female
/ Gene expression
/ Gene Expression Profiling
/ Gene Expression Regulation, Neoplastic
/ Growth factors
/ Humans
/ Immunotherapy
/ liquid-liquid phase separation
/ Male
/ Medical prognosis
/ membraneless organelle
/ methylation
/ Microenvironments
/ Neuregulin-1 - genetics
/ Neuregulin-1 - metabolism
/ Nrg1
/ Organelles
/ Pathogenesis
/ Patients
/ Principal components analysis
/ Prognosis
/ Promoter Regions, Genetic
/ Proteins
/ Survival analysis
/ Transcriptome
/ Transcriptomics
/ Tumor Microenvironment - immunology
/ Tumorigenesis
2025
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Membraneless organelles-based integrative analysis constructs an immune-related prognostic signature and identifies NRG1 as a novel methylation biomarker in colorectal cancer
by
Cheng, Jingsong
, Luo, Siqi
, Liu, Guodong
, Chen, Weilong
, Zhu, Xinyi
, Yin, Qingyao
, Chen, Xue
, Wang, Ningxi
, Zhang, Chengxi
, Luo, Rugang
, Zheng, Ziheng
, Wan, Yuanyuan
, Chen, Nanting
in
Algorithms
/ Biomarkers
/ Biomarkers, Tumor - genetics
/ Cell Line, Tumor
/ Chemotherapy
/ Clinical outcomes
/ Colorectal cancer
/ Colorectal carcinoma
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - immunology
/ Colorectal Neoplasms - metabolism
/ Colorectal Neoplasms - mortality
/ Colorectal Neoplasms - pathology
/ Datasets
/ DNA Methylation
/ Down-regulation
/ Ecotypes
/ Female
/ Gene expression
/ Gene Expression Profiling
/ Gene Expression Regulation, Neoplastic
/ Growth factors
/ Humans
/ Immunotherapy
/ liquid-liquid phase separation
/ Male
/ Medical prognosis
/ membraneless organelle
/ methylation
/ Microenvironments
/ Neuregulin-1 - genetics
/ Neuregulin-1 - metabolism
/ Nrg1
/ Organelles
/ Pathogenesis
/ Patients
/ Principal components analysis
/ Prognosis
/ Promoter Regions, Genetic
/ Proteins
/ Survival analysis
/ Transcriptome
/ Transcriptomics
/ Tumor Microenvironment - immunology
/ Tumorigenesis
2025
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Membraneless organelles-based integrative analysis constructs an immune-related prognostic signature and identifies NRG1 as a novel methylation biomarker in colorectal cancer
Journal Article
Membraneless organelles-based integrative analysis constructs an immune-related prognostic signature and identifies NRG1 as a novel methylation biomarker in colorectal cancer
2025
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Overview
The dysfunction of membraneless organelles (MLOs) has been implicated in tumorigenesis and progression by aberrant liquid-liquid phase separation (LLPS). However, the role of MLOs in the prognosis and tumor immune microenvironment (TIME) of colorectal cancer (CRC) remains unclear.
We integrated transcriptomic data of MLO-related genes to identify distinct CRC subtypes and constructed a prognostic risk score termed MPRS. Then, we systematically demonstrated the characteristics of MPRS based on multi-omics analyses. We further assessed NRG1's LLPS possibility, prognostic significance, and its correlation with methylation through comprehensive analysis and
experiment.
A prognostic signature called MPRS associated with prognosis, tumor ecotypes, genomic alterations, TIME patterns, immunotherapy responses, chemotherapy sensitivity in CRC patients. NRG1, identified as the most important MPRS gene with high predicted LLPS propensity-was significantly downregulated in CRC tissues and correlated with prognosis. Promoter methylation was found to be a crucial mechanism underlying NRG1 downregulation, which could be rescued by 5-Aza-2-deoxycytidine (Aza) treatment. The qRT-PCR, IHC and Aza treatment were utilized for
validation.
Our integrated multi-omics analysis constructed the MPRS model to delineate CRC tumor ecology and identified NRG1 as a methylation biomarker with predicted phase-separation propensity, with potential therapeutic implications that warrant prospective validation.
Publisher
Frontiers Media SA,Frontiers Media S.A
Subject
/ Biomarkers, Tumor - genetics
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - immunology
/ Colorectal Neoplasms - metabolism
/ Colorectal Neoplasms - mortality
/ Colorectal Neoplasms - pathology
/ Datasets
/ Ecotypes
/ Female
/ Gene Expression Regulation, Neoplastic
/ Humans
/ liquid-liquid phase separation
/ Male
/ Nrg1
/ Patients
/ Principal components analysis
/ Proteins
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