Table 1_A novel liquid-liquid phase separation-related gene signature for predicting prognosis in colon cancer.xlsx

BackgroundAn increasing body of evidence indicates that dysregulation of liquid-liquid phase separation (LLPS) in cellular processes is implicated in the development of diverse tumors. Nevertheless, the association between LLPS and the prognosis, as well as the tumor immune microenvironment, in individuals with colon cancer remains poorly understood.
MethodsWe conducted a comprehensive evaluation of the LLPS cluster in 1010 colon cancer samples from the TCGA and GEO databases, utilizing the expression profiles of LLPS-related prognostic differentially expressed genes (DEGs). Subsequently, a LLPS-related gene signature was constructed to calculate the LLPS-related risk score (LRRS) for each individual patient.
ResultsTwo LLPS subtypes were identified. Substantial variations were observed between the two LLPS subtypes in terms of prognosis, pathway activity, clinicopathological characteristics, and immune characteristics. Patients with high LRRS exhibited worse prognosis and poorer response to immunotherapy. LRRS was found to be correlated with the clinicopathological characteristics, genomic alterations, and the potential response to immune checkpoint inhibitors therapy of colon cancer patients. Additionally, the biological function of a key gene POU4F1 was verified in vitro.
ConclusionsThis study highlights the crucial role of LLPS in colon cancer, LRRS can be used to predict the prognosis of colon cancer patients and aid in the identification of more effective immunotherapy strategies.

背景
越来越多的研究证据表明，细胞进程中的液-液相分离（liquid-liquid phase separation, LLPS）失调与多种肿瘤的发生发展密切相关。然而，结肠癌患者体内LLPS与预后及肿瘤免疫微环境之间的关联仍不甚明晰。

方法
本研究借助LLPS相关预后差异表达基因（differentially expressed genes, DEGs）的表达谱，对来自癌症基因组图谱（The Cancer Genome Atlas, TCGA）与基因表达综合数据库（Gene Expression Omnibus, GEO）的1010例结肠癌样本的LLPS分型展开全面评估。随后构建LLPS相关基因特征模型，以计算每名患者的LLPS相关风险评分（LLPS-related risk score, LRRS）。

结果
本研究共鉴定出两类LLPS亚型。两类LLPS亚型在预后情况、通路活性、临床病理特征及免疫特征层面均存在显著差异。LRRS评分较高的患者预后更差，且对免疫治疗的应答不佳。进一步分析显示，LRRS与结肠癌患者的临床病理特征、基因组变异以及免疫检查点抑制剂治疗的潜在应答水平均存在相关性。此外，本研究通过体外实验验证了关键基因POU4F1的生物学功能。

结论
本研究凸显了LLPS在结肠癌发生发展中的关键调控作用，LRRS可用于预测结肠癌患者的预后，同时有助于筛选更为精准有效的免疫治疗策略。