Risk model of liquid–liquid phase separation‐related genes reveals the prognosis and tumor microenvironment characteristics of colorectal cancer
Year: 2025
Type: article
Abstract: Colorectal cancer (CRC) progression involves liquid-liquid phase separation (LLPS), but its prognostic significance remains unexplored. Using The Cancer Genome Atlas transcriptomic data, we developed an LLPS-based risk model that outperformed traditional clustering methods. High-risk patients exhibited worse outcomes, correlating with higher tumor mutational burden and reduced natural killer/T-cell infiltration, yet increased predicted response to immune checkpoint blockade. Drug sensitivity analysis suggested therapeutic efficacy of Entinostat and 5-fluorouracil in this subgroup. Five pivotal genes (ASXL1, DDX21, HNRNPA1L2, TACC3, and TRIM28) were identified as LLPS-driven regulators of CRC progression, mechanistically linking phase separation to epigenetic dysregulation, aberrant RNA splicing, and metabolic reprogramming. Our study provides the first LLPS-associated prognostic framework for CRC, offering both a risk stratification tool and actionable therapeutic insights. The findings highlight LLPS as a critical molecular organizer in CRC pathogenesis and a potential target for precision oncology approaches.
DOI: 10.1002/ccs3.70054
Authors: Hui Liu, Ziwen Chen, Jie Hao, Ziyi Dong, Yaoyang Guo, Minghan Qiu, Xipeng Zhang, Ming Gao, Haiyang Zhang, Mingqing Zhang
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $2,860
Funders: Beijing Rong He Medical Development Foundation, Natural Science Foundation of Tianjin City, Tianjin Science and Technology Committee, Tianjin Municipal Bureau of Public Health, Tianjin Municipal Education Commission, Natural Science Foundation of Tianjin Municipal Science and Technology Commission, Tianjin Science and Technology Program
OpenAlex ID: W4415835654