Liu Jinhui, Chen Can, Geng Rui, Shao Fang, Yang Sheng, Zhong Zihang, Ni Senmiao, Bai Jianling
Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing 210029, Jiangsu Province, China.
Comput Struct Biotechnol J. 2022 Sep 28;20:5440-5452. doi: 10.1016/j.csbj.2022.09.037. eCollection 2022.
Pyroptosis, a form of inflammatory programmed cell death, is accompanied by inflammation and participate in the body's immune response. The expression of pyroptosis-related genes (PRGs) is associated with tumor prognosis in ovarian cancer (OC), but it is still unknown whether pyroptosis can affect tumor immune microenvironment (TME) of OC. Based on 30 PRGs, we comprehensively assessed the pyroptosis patterns by using PRGscore and correlated them with TME features in 474 OC patients. Finally, we identified three pyroptosis modification patterns and TME immune characteristics of these patterns were in response to three immune phenotypes (immune-desert, immune-inflamed, and immune-excluded phenotypes). PRGscore can predict patient survival, staging, grading, and immunotherapy efficacy. Low PRGscore was associated with better survival advantage and increased mutation burden. Low PRGscore patients showed significantly better therapeutic effects and clinical results in chemotherapy and immunotherapy. Besides, the capability of PRGscore in predicting prognosis and immunotherapy sensitivity was further verified in other three tumor cohorts. In conclusion, the comprehensive assessment of OC pyroptosis modifications can help enhancing our understanding of TME immune infiltration and provide better personalized treatment tactics for OC patients.
细胞焦亡是一种炎症性程序性细胞死亡形式,伴有炎症反应并参与机体免疫反应。细胞焦亡相关基因(PRGs)的表达与卵巢癌(OC)的肿瘤预后相关,但细胞焦亡是否会影响OC的肿瘤免疫微环境(TME)仍不清楚。基于30个PRGs,我们使用PRGscore全面评估了细胞焦亡模式,并将其与474例OC患者的TME特征相关联。最后,我们确定了三种细胞焦亡修饰模式,这些模式的TME免疫特征与三种免疫表型(免疫沙漠型、免疫炎症型和免疫排除型)相对应。PRGscore可以预测患者的生存、分期、分级和免疫治疗疗效。低PRGscore与更好的生存优势和增加的突变负担相关。低PRGscore患者在化疗和免疫治疗中显示出显著更好的治疗效果和临床结果。此外,PRGscore在预测其他三个肿瘤队列的预后和免疫治疗敏感性方面的能力得到了进一步验证。总之,对OC细胞焦亡修饰的全面评估有助于增强我们对TME免疫浸润的理解,并为OC患者提供更好的个性化治疗策略。