研究动态
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在卵巢癌的预后和免疫治疗中,识别和验证与火凤燎症相关的基因景观。

Identification and validation of pyroptosis-related gene landscape in prognosis and immunotherapy of ovarian cancer.

发表日期:2023 Jan 27
作者: Lingling Gao, Feiquan Ying, Jing Cai, Minggang Peng, Man Xiao, Si Sun, Ya Zeng, Zhoufang Xiong, Liqiong Cai, Rui Gao, Zehua Wang
来源: Journal of Ovarian Research

摘要:

新兴证据强调了细胞威瑞森病在肿瘤发生和进展中的生物学意义。然而,细胞威瑞森病在卵巢癌的免疫微环境及靶向治疗中的潜在作用仍未知晓。本研究采用一系列生物信息学和机器学习方法,全面评估了TCGA-OV数据库中细胞威瑞森病相关基因(PYAGs)的遗传变异和转录组特征。进行一致性分子聚类以确定细胞威瑞森病相关簇(PACs)和卵巢癌基因簇。随后,采用组分分析算法(PCA)构建Pyrsig评分,并建立了高度准确的评分图来评估其功效。同时,我们系统性地分析了这些组与预后、临床特征、TME细胞浸润特征、药物反应和免疫治疗效果之间的关联。还进行免疫组织化学实验验证了临床样本中的分子表达。澄清了51个PYRGs基因在OC样本中的体细胞突变和拷贝数变异(CNV)。基于1332个OC样本,鉴定出两个不同的PACs(PAC1 / 2)和三个基因簇(A / B / C)。PAC1和基因簇A与良好的总生存率(OS)、临床病理特征和TME细胞浸润特征显著相关。随后,成功建立了Pyrsig评分,以显示细胞威瑞森病在OC中的预后价值和免疫特征,低Pyrsig评分,其特点为激活的免疫细胞浸润,预示着延长生存期、提高某些化疗药物的敏感性、增强抗PD-L1免疫治疗的效果。因此,成功建立了一个评分图,以提高Pyrsig评分的临床适用性和稳定性。用OC临床样本验证了GSDMD和GZMB蛋白在OC中高表达,并与免疫浸润和Pyrsig评分相关,GZMB和CD8蛋白被认为是OC的独立预后因素。本研究揭示了细胞威瑞森病在OC中在预后价值、临床病理特征和肿瘤免疫浸润微环境中发挥着不可忽视的作用,为鉴定和表征肿瘤免疫微环境的统景开了新的视角,从而指导OC更有效的预后评估和个体化免疫治疗策略。 © 2023. 作者。
Emerging evidence has highlighted the biological significance of pyroptosis in tumor tumorigenesis and progression. Nonetheless, the potential roles of pyroptosis in tumor immune microenvironment and target therapy of ovarian cancer (OC) remain unknown.In this study, with a series of bioinformatic and machine learning approaches, we comprehensively evaluated genetic alterations and transcriptome profiles of pyroptosis-associated genes (PYAGs) with TCGA-OV datasets. Consensus molecular clustering was performed to determine pyroptosis-associated clusters (PACs) and gene clusters in OC. Subsequently, component analysis algorithm (PCA) was employed to construct Pyrsig score and a highly accurate nomogram was established to evaluate its efficacy. Meanwhile, we systematically performed association analysis for these groups with prognosis, clinical features, TME cell-infiltrating characteristics, drug response and immunotherapeutic efficacy. Immunohistochemistry was conducted to verify molecular expression with clinical samples.The somatic mutations and copy number variation (CNV) of 51 PYRGs in OC samples were clarified. Two distinct PACs (PAC1/2) and three gene clusters (A/B/C) were identified based on 1332 OC samples, PAC1 and gene cluster A were significantly associated with favorable overall survival (OS), clinicopathological features and TME cell-infiltrating characteristics. Subsequently, Pyrsig score was successfully established to demonstrate the prognostic value and immune characteristics of pyroptosis in OC, low Pyrsig score, characterized by activated immune cell infiltration, indicated prolonged OS, increased sensitivity of some chemotherapeutic drugs and enhanced efficacy of anti-PD-L1 immunotherapy, Consequently, a nomogram was successfully established to improve the clinical applicability and stability of Pyrsig score. With clinical OC samples, GSDMD and GZMB proteins were validated highly expressed in OC and associated with immune infiltration and Pyrsig score, GZMB and CD8 proteins were regarded as independent prognostic factors of OC.This work revealed pyroptosis played a non-negligible role in prognosis value, clinicopathological characteristics and tumor immune infiltration microenvironment in OC, which provided novel insights into identifying and characterizing landscape of tumor immune microenvironment, thereby guiding more effective prognostic evaluation and tailored immunotherapy strategies of OC.© 2023. The Author(s).