结肠癌的细胞焦亡模式有助于评估预后、微环境和免疫治疗:来自多组学分析的证据。

Pyroptosis patterns of colon cancer could aid to estimate prognosis, microenvironment and immunotherapy: evidence from multi-omics analysis.

机构信息

Department of Oncology, Shanxi Province Academy of Traditional Chinese Medicine, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, Shanxi 030012, China.

Shanxi Clinical Research Center of Traditional Chinese Medicine Affiliated Shanxi Hospital of TCM, Taiyuan, Shanxi 030012, China.

出版信息

Aging (Albany NY). 2022 Sep 23;14(18):7547-7567. doi: 10.18632/aging.204302.

Abstract

Pyroptosis plays a critical role in the occurrence and development of colon cancer (CC). However, the specific mechanisms of pyroptosis patterns on immune regulation and tumor microenvironment (TME) formation in CC remain unclear. Based on 30 pyroptosis-related genes (PRGs), we evaluated the pyroptosis patterns of 1689 CC samples from the Cancer Genome Atlas and the Gene Expression Omnibus databases. The signatures of pyroptosis patterns and PRGs were identified in CC. In addition to systematically associating these patterns with TME cell infiltration characteristics, we constructed a pyroptosis signature score (PPSscore) to quantify pyroptosis patterns in individual tumor patients with immune responses. We discovered three distinct pyroptosis patterns, each with a different survival probability and being biologically relevant. TME infiltrating characteristics of revealed these patterns, consistent with immune-inflamed, immune-desert and immune-excluded phenotypes. Furthermore, a low PPSscore was associated with better clinical benefits. A high PPSscore was associated with a lower chance of survival due to its association with stromal activation. Additionally, two immunotherapy cohorts revealed that patients with lower PPSscore had better immune responses and durable clinical benefits. Our findings indicate that pyroptosis patterns play a vital role in immunoregulation and the formation of TME in CC.

摘要

细胞焦亡在结肠癌(CC)的发生和发展中起着关键作用。然而,细胞焦亡模式对 CC 中免疫调节和肿瘤微环境(TME)形成的具体机制仍不清楚。基于 30 个细胞焦亡相关基因(PRGs),我们评估了来自癌症基因组图谱和基因表达综合数据库的 1689 个 CC 样本的细胞焦亡模式。鉴定了 CC 中细胞焦亡模式和 PRGs 的特征。除了系统地将这些模式与 TME 细胞浸润特征相关联外,我们还构建了一个细胞焦亡特征评分(PPSscore)来量化个体肿瘤患者的免疫反应中的细胞焦亡模式。我们发现了三种不同的细胞焦亡模式,每种模式都有不同的生存概率和生物学相关性。揭示这些模式的 TME 浸润特征与免疫炎症、免疫荒漠和免疫排斥表型一致。此外,低 PPSscore 与更好的临床获益相关。由于与基质激活相关,高 PPSscore 与较低的生存机会相关。此外,两个免疫治疗队列表明,PPSscore 较低的患者具有更好的免疫反应和持久的临床获益。我们的研究结果表明,细胞焦亡模式在 CC 中的免疫调节和 TME 形成中起着至关重要的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/380a/9550258/8cc8f69cd60f/aging-14-204302-g001.jpg

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