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解析结肠癌中与焦亡相关的预后特征及免疫细胞浸润特性

Deciphering the Pyroptosis-Related Prognostic Signature and Immune Cell Infiltration Characteristics of Colon Cancer.

作者信息

Wei Ran, Li Shuofeng, Yu Guanhua, Guan Xu, Liu Hengchang, Quan Jichuan, Jiang Zheng, Wang Xishan

机构信息

Department of Colorectal Cancer Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Front Genet. 2021 Oct 12;12:755384. doi: 10.3389/fgene.2021.755384. eCollection 2021.

Abstract

Colon cancer (CC) remains one of the most common malignancies with a poor prognosis. Pyroptosis, referred to as cellular inflammatory necrosis, is thought to influence tumor development. However, the potential effects of pyroptosis-related regulators (PRRs) on the CC immune microenvironment remain unknown. In this study, 27 PRRs reported in the previous study were used to cluster the 1,334 CC samples into three pyroptosis-related molecular patterns. Through subtype pattern differential analysis and structure network mining using Weighted Gene Co-expression Network Analysis (WGCNA), 854 signature genes associated with the PRRs were discovered. Further LASSO-penalized Cox regression of these genes established an eight-gene assessment model for predicting prognosis. The CC patients were subtyped based on three distinct pyroptosis-related molecular patterns. These pyroptosis-related patterns were correlated with different clinical outcomes and immune cell infiltration characteristics in the tumor microenvironment. The pyroptosis-related eight-signature model was established and used to assess the prognosis of CC patients with medium-to-high accuracy by employing the risk scores, which was named "PRM-scores." Greater inflammatory cell infiltration was observed in tumors with low PRM-scores, indicating a potential benefit of immunotherapy in these patients. This study suggests that PRRs have a significant effect on the tumor immune microenvironment and tumor development. Evaluating the pyroptosis-related patterns and related models will promote our understanding of immune cell infiltration characteristics in the tumor microenvironment and provide a theoretical basis for future research targeting pyroptosis in cancer.

摘要

结肠癌(CC)仍然是最常见的恶性肿瘤之一,预后较差。细胞焦亡,即细胞炎性坏死,被认为会影响肿瘤的发展。然而,细胞焦亡相关调节因子(PRRs)对CC免疫微环境的潜在影响仍不清楚。在本研究中,利用先前研究报道的27个PRRs将1334个CC样本聚类为三种与细胞焦亡相关的分子模式。通过使用加权基因共表达网络分析(WGCNA)进行亚型模式差异分析和结构网络挖掘,发现了854个与PRRs相关的特征基因。对这些基因进行进一步的LASSO惩罚Cox回归,建立了一个用于预测预后的八基因评估模型。CC患者根据三种不同的与细胞焦亡相关的分子模式进行亚型分类。这些与细胞焦亡相关的模式与不同的临床结果以及肿瘤微环境中的免疫细胞浸润特征相关。建立了与细胞焦亡相关的八特征模型,并通过使用风险评分(命名为“PRM评分”)以中等至高准确率评估CC患者的预后。在PRM评分低的肿瘤中观察到更大程度的炎性细胞浸润,表明这些患者可能从免疫治疗中获益。本研究表明,PRRs对肿瘤免疫微环境和肿瘤发展有显著影响。评估与细胞焦亡相关的模式和相关模型将促进我们对肿瘤微环境中免疫细胞浸润特征的理解,并为未来针对癌症细胞焦亡的研究提供理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a60/8546261/8ae65ce2e844/fgene-12-755384-g001.jpg

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