PDF(Pubmed)
Abstract：
Anoikis is highly associated with tumor cell apoptosis and tumor prognosis; however, the specific role of anoikis-related genes (ARGs) in soft tissue sarcoma (STS) remains to be fully elucidated. The present study aimed to use a variety of bioinformatics methods to determine differentially expressed anoikis-related genes in STS and healthy tissues. Subsequently, three machine learning algorithms, Least Absolute Shrinkage and Selection Operator, Support Vector Machine and Random Forest, were used to screen genes with the highest importance score. The results of the bioinformatics analyses demonstrated that CASP8 and FADD-like apoptosis regulator (CFLAR) exhibited the highest importance score. Subsequently, the diagnostic and prognostic value of CFLAR in STS development was determined using multiple public and in-house cohorts. The results of the present study demonstrated that CFLAR may be considered a diagnostic and prognostic marker of STS, which acts as an independent prognostic factor of STS development. The present study also aimed to explore the potential role of CFLAR in the STS tumor microenvironment, and the results demonstrated that CFLAR significantly enhanced the immune response of STS, and exerted a positive effect on the infiltration of CD8+ T cells and M1 macrophages in the STS immune microenvironment. Notably, the aforementioned results were verified using multiplex immunofluorescence analysis. Collectively, the results of the present study demonstrated that CFLAR may act as a novel diagnostic and prognostic marker for STS, and may positively regulate the immune response of STS. Thus, the present study provided a novel theoretical basis for the use of CFLAR in STS diagnosis, in predicting clinical outcomes and in tailoring individualized treatment options.
摘要：
Anoikis与肿瘤细胞凋亡和肿瘤预后密切相关；然而，失巢凋亡相关基因（ARGs）在软组织肉瘤（STS）中的具体作用仍有待完全阐明。本研究旨在利用多种生物信息学方法确定STS和健康组织中差异表达的失巢凋亡相关基因。随后，三种机器学习算法，最小绝对收缩和选择算子，支持向量机与随机森林,用于筛选重要性得分最高的基因。生物信息学分析的结果表明，CASP8和FADD样凋亡调节因子（CFLAR）表现出最高的重要性得分。随后，CFLAR在STS发展中的诊断和预后价值是使用多个公共和内部队列确定的.本研究的结果表明，CFLAR可以被认为是STS的诊断和预后标志物。作为STS发展的独立预后因素。本研究还旨在探讨CFLAR在STS肿瘤微环境中的潜在作用。结果表明，CFLAR显着增强了STS的免疫反应，并对STS免疫微环境中CD8+T细胞和M1巨噬细胞的浸润产生积极影响。值得注意的是,上述结果使用多重免疫荧光分析进行了验证。总的来说，本研究的结果表明，CFLAR可以作为STS的一种新的诊断和预后标志物，并可能积极调节STS的免疫反应。因此，本研究为CFLAR在STS诊断中的应用提供了新的理论基础,预测临床结局和定制个性化治疗方案。
