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一种用于预测结肠癌预后的新型液-液相分离相关基因特征。

A novel liquid-liquid phase separation-related gene signature for predicting prognosis in colon cancer.

作者信息

Wang Shuo, Hou Sen, Jiang Shan, Wang Chao, Zhang Peipei, Ye Yingjiang, Gao Zhidong

机构信息

Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China.

Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, China.

出版信息

Front Immunol. 2024 Dec 19;15:1514613. doi: 10.3389/fimmu.2024.1514613. eCollection 2024.

DOI:10.3389/fimmu.2024.1514613
PMID:39749343
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11693697/
Abstract

BACKGROUND

An 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.

METHODS

We 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.

RESULTS

Two 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 .

CONCLUSIONS

This 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.

摘要

背景

越来越多的证据表明，细胞过程中液-液相分离（LLPS）的失调与多种肿瘤的发生发展有关。然而，LLPS与结肠癌患者预后以及肿瘤免疫微环境之间的关联仍知之甚少。

方法

我们利用LLPS相关预后差异表达基因（DEG）的表达谱，对来自TCGA和GEO数据库的1010例结肠癌样本中的LLPS簇进行了综合评估。随后，构建了一个LLPS相关基因特征，以计算每个患者的LLPS相关风险评分（LRRS）。

结果

鉴定出两种LLPS亚型。在预后、通路活性、临床病理特征和免疫特征方面，两种LLPS亚型之间存在显著差异。LRRS高的患者预后较差，对免疫治疗的反应也较差。发现LRRS与结肠癌患者的临床病理特征、基因组改变以及对免疫检查点抑制剂治疗的潜在反应相关。此外，关键基因POU4F1的生物学功能得到了验证。

结论

本研究强调了LLPS在结肠癌中的关键作用，LRRS可用于预测结肠癌患者的预后，并有助于确定更有效的免疫治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2c6/11693697/1ececf3e9fcf/fimmu-15-1514613-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2c6/11693697/681ba60d9af0/fimmu-15-1514613-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2c6/11693697/5680e8f00dbe/fimmu-15-1514613-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2c6/11693697/8cf43975d031/fimmu-15-1514613-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2c6/11693697/1ececf3e9fcf/fimmu-15-1514613-g010.jpg

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