Department of Anorectal Surgery, Jiaxing Second Hospital, Jiaxing 314000, Zhejiang, P.R. China.
Department of Gastrointestinal Surgery, Jiaxing Second Hospital, Jiaxing 314000, Zhejiang, P.R. China.
Aging (Albany NY). 2022 Nov 16;14(22):9020-9036. doi: 10.18632/aging.204379.
The important role of pyroptosis in tumor progression has been well characterized in recent years. However, little is known about the impact of tumor pyroptosis characteristics on patient prognosis and tumor microenvironment (TME) as well as efficacy of immunotherapy. In this study, we successfully classified colon cancer samples into three pyroptosis characterizations with different prognosis and TME cell infiltration patterns based on the expression of pyroptosis-related genes. Cluster 2, with the characterizations of immunosuppression, was classified as immune-desert cell infiltration patterns. Cluster 3, with the patterns of immune-inflamed cell infiltration, had the feature of an activated innate and adaptive immunity and significant prolonged survival. The activation of stromal pathways including EMT, angiogenesis and TGF-β in cluster 1 may mediate the impaired immune penetration of this cluster, which was classified as immune-excluded cell infiltration patterns. Our results demonstrated the PyroSig signature was a robust and independent biomarker for predicting patient prognosis. Patients with low PyroSig signature was confirmed to be correlated with treatment advantages and significant prolonged survival in two anti-checkpoint immunotherapy cohorts. This study identified three pyroptosis-related subtypes with distinct molecular features, clinical and microenvironment cell infiltration patterns in colon cancer, which could promote individualized immunotherapy for colon cancer.
近年来，细胞焦亡在肿瘤进展中的重要作用得到了很好的描述。然而，人们对肿瘤细胞焦亡特征对患者预后和肿瘤微环境（TME）以及免疫治疗效果的影响知之甚少。在这项研究中，我们成功地根据细胞焦亡相关基因的表达，将结肠癌样本分为具有不同预后和 TME 细胞浸润模式的三种细胞焦亡特征。具有免疫抑制特征的簇 2 被归类为免疫荒漠细胞浸润模式。簇 3 具有免疫炎症细胞浸润模式，其特点是先天和适应性免疫激活，并且显著延长了生存时间。簇 1 中包括 EMT、血管生成和 TGF-β 在内的基质途径的激活可能介导了该簇免疫穿透受损，被归类为免疫排斥细胞浸润模式。我们的研究结果表明，PyroSig 特征是预测患者预后的稳健且独立的生物标志物。在两个抗检查点免疫治疗队列中，低 PyroSig 特征的患者被证实与治疗优势和显著延长的生存时间相关。本研究在结肠癌中确定了三种具有不同分子特征、临床和微环境细胞浸润模式的细胞焦亡相关亚型，可为结肠癌的个体化免疫治疗提供依据。
