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鉴定与宫颈癌发生和预后相关的关键免疫细胞相关基因。

Identification of key immune cell-related genes involved in tumorigenesis and prognosis of cervical squamous cell carcinoma.

机构信息

School of Medicine, Department of Gynecology, The Second Affiliated Hospital of Zhejiang University, Hangzhou, China.

出版信息

Hum Vaccin Immunother. 2023 Aug;19(2):2254239. doi: 10.1080/21645515.2023.2254239. Epub 2023 Oct 6.

DOI:10.1080/21645515.2023.2254239
PMID:37799074
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10561582/
Abstract

The infiltration of immune cells can significantly affect the prognosis and immune therapy of patients with cervical squamous cell carcinoma (CSCC). This study aimed to explore key immune cell-related genes in the tumorigenesis and prognosis of CSCC. The module significantly related to immunity was screened by weighted gene co-expression network analysis (WGCNA) and ESTIMATE analysis, followed by correlation analysis with clinical traits. Key candidate genes were intersected with the protein-protein interaction (PPI) network genes for immune-related genes. The relationship between immune cell infiltration and key genes was analyzed. Tumor immune dysfunction and exclusion (TIDE) and immunophenoscore (IPS) predicted the response to immunotherapy in CSCC patients. Clinically, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry were manipulated for analyzing the changes in mRNA and protein expression of key genes in cancer. Western blot was conducted to assess the correlation between key genes and immune infiltration. The brown module was notably associated with the immune microenvironment of CSCC, from which three immune-related key genes (, , and ) were obtained. High expression of these genes was significantly positively associated with the infiltration abundance of T cells, B cells, and other immune cells. High expression levels of three key genes were confirmed in para-cancer tissue and correlated with the abundance of immune cells. The high-expression group of key genes was more sensitive to immunotherapy. We provide a theoretical basis for searching for potential targets for effective treatment and diagnosis of CSCC and provide new ideas for developing novel immunotherapy strategies.

摘要

免疫细胞的浸润可以显著影响宫颈鳞状细胞癌 (CSCC) 患者的预后和免疫治疗。本研究旨在探讨与 CSCC 发生和预后相关的关键免疫细胞相关基因。通过加权基因共表达网络分析 (WGCNA) 和 ESTIMATE 分析筛选与免疫显著相关的模块,然后与临床特征进行相关性分析。将关键候选基因与蛋白质-蛋白质相互作用 (PPI) 网络基因进行免疫相关基因的交集。分析免疫细胞浸润与关键基因的关系。肿瘤免疫功能障碍和排斥 (TIDE) 和免疫表型评分 (IPS) 预测 CSCC 患者对免疫治疗的反应。临床上,通过定量实时聚合酶链反应 (qRT-PCR) 和免疫组织化学分析癌症中关键基因的 mRNA 和蛋白表达变化。Western blot 用于评估关键基因与免疫浸润之间的相关性。棕色模块与 CSCC 的免疫微环境显著相关,从中获得了三个与免疫相关的关键基因 (,, 和 )。这些基因的高表达与 T 细胞、B 细胞和其他免疫细胞的浸润丰度呈显著正相关。在癌旁组织中证实了三个关键基因的高表达水平,并与免疫细胞的丰度相关。关键基因高表达组对免疫治疗更敏感。我们为寻找 CSCC 有效治疗和诊断的潜在靶点提供了理论依据,并为开发新的免疫治疗策略提供了新的思路。

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