宫颈癌的Anoikis模式:亚群的鉴定和预测预后和免疫反应的新风险模型的构建

Xuesong Xiang, Jingxin Ding
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摘要

背景:宫颈癌具有高发病率和肿瘤内异质性。Anoikis是一种程序性细胞死亡的形式,可以防止分离的癌细胞读取,可能是宫颈癌的潜在预后标志。本研究旨在评估anoikis模式对宫颈癌预后的预测作用。方法:利用基因表达综合数据库(Gene Expression Omnibus)的数据,在正常和癌症样本中鉴定差异表达的气味相关基因(DEARGs),并阐明其突变状态和生物功能。通过一致聚类分析,在癌症基因组图谱(TCGA)队列中定义了新的anoikis分子亚型。通过最小绝对收缩和选择算子(LASSO) Cox分析构建多基因预后特征,并进行内部和外部验证。通过校准、受试者工作特征、决策曲线分析和Kaplan-Meier曲线预测和评估宫颈癌3年和5年生存率。此外,对不同风险组进行突变、功能和免疫分析。结果:我们在正常和宫颈癌组织中鉴定了77个DEARGs,并探讨了它们的突变状态和功能。TCGA队列可以根据这些基因分为两个亚型。此外,构建了7个预后特征基因,涉及DEARGs和临床病理特征的nomogram预后预测图显示了令人满意的预测效果。功能分析表明免疫相关基因丰富,免疫状态、化疗和靶向药物敏感性与风险模型相关。结论:Anoikis在肿瘤免疫中起重要作用,可用于预测宫颈癌的预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Anoikis Patterns in Cervical Cancer: Identification of Subgroups and Construction of a Novel Risk Model for Predicting Prognosis and Immune Response
Background: Cervical cancer has high morbidity and intratumor heterogeneity. Anoikis, a form of programmed cell death preventing detached cancer cells from readhering, may serve as a potential prognostic signature for cervical cancer. This study aimed to assess the predictive performance of anoikis patterns in cervical cancer prognosis. Methods: Differentially expressed anoikis-related genes (DEARGs) were identified between normal and cancer samples using data from the Gene Expression Omnibus database with the elucidation of mutation status and bio-function. Novel anoikis molecular subtypes were defined in The Cancer Genome Atlas (TCGA) cohort with consensus clustering analysis. A multigene prognostic signature was constructed through least absolute shrinkage and selection operator (LASSO) Cox analysis with internal and external validation. The nomogram-based survival probability of cervical cancer over 3 and 5 years was predicted and assessed with calibration, receiver operating characteristic, decision curve analysis, and Kaplan-Meier curves. Additionally, mutation, function, and immune analysis were conducted among different risk groups. Results: We identified 77 DEARGs between normal and cervical cancer tissues and explored their mutation status and functions. The TCGA cohort could be categorized into two subtypes based on these genes. Furthermore, seven prognostic signature genes were constructed, and the nomogram involving DEARGs and clinicopathological characteristics showed satisfactory predictive performance. Functional analysis indicated that immune-related genes were enriched, and immune status, as well as sensitivity of chemotherapies and targeting drugs, were correlated with the risk model. Conclusions: Anoikis patterns play important roles in tumor immunity and can be used to predict the prognosis of cervical cancers.
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