液-液相分离相关基因的风险模型揭示了结直肠癌的预后和肿瘤微环境特征

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.