Shen Jiacheng, Liu Tingwei, Lv Jia, Xu Shaohua
Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Front Cell Dev Biol. 2021 Oct 12;9:746932. doi: 10.3389/fcell.2021.746932. eCollection 2021.
To understand the immune characteristics of the ovarian cancer (OC) microenvironment and explore the differences of immune-related molecules and cells to establish an effective risk model and identify the molecules that significantly affected the immune response of OC, to help guide the diagnosis. First, we calculate the TMEscore which reflects the immune microenvironment, and then analyze the molecular differences between patients with different immune characteristics, and determine the prognostic genes. Then, the risk model was established by least absolute shrinkage and selection operator (LASSO) analysis and combined with clinical data into a nomogram for diagnosis and prediction. Subsequently, the potential gene CLEC5A influencing the immune response of OC was identified from the prognostic genes by integrative immune-stromal analysis. The genomic alteration was explored based on copy number variant (CNV) and somatic mutation data. TMEscore was a prognostic indicator of OC. The prognosis of patients with high TMEscore was better. The risk model based on immune characteristics was a reliable index to predict the prognosis of patients, and the nomogram could comprehensively evaluate the prognosis of patients. Besides, CLEC5A was closely related to the abundance of immune cells, immune response, and the expression of immune checkpoints in the OC microenvironment. OC cells with high expression of CLEC5A increased the polarization of M2 macrophages. CLEC5A expression was significantly associated with TTN and CDK12 mutations and affected the copy number of tumor progression and immune-related genes. The study of immune characteristics in the OC microenvironment and the risk model can reveal the factors affecting the prognosis and guide the clinical hierarchical treatment. CLEC5A can be used as a potential key gene affecting the immune microenvironment remodeling of OC, which provides a new perspective for improving the effect of OC immunotherapy.
为了解卵巢癌（OC）微环境的免疫特征，探索免疫相关分子和细胞的差异，建立有效的风险模型并识别显著影响OC免疫反应的分子，以辅助指导诊断。首先，我们计算反映免疫微环境的TMEscore，然后分析不同免疫特征患者之间的分子差异，确定预后基因。接着，通过最小绝对收缩和选择算子（LASSO）分析建立风险模型，并结合临床数据制成列线图用于诊断和预测。随后，通过综合免疫-基质分析从预后基因中鉴定出影响OC免疫反应的潜在基因CLEC5A。基于拷贝数变异（CNV）和体细胞突变数据探索基因组改变。TMEscore是OC的一个预后指标。TMEscore高的患者预后较好。基于免疫特征的风险模型是预测患者预后的可靠指标，列线图可全面评估患者预后。此外，CLEC5A与OC微环境中免疫细胞的丰度、免疫反应及免疫检查点的表达密切相关。CLEC5A高表达的OC细胞增加M2巨噬细胞的极化。CLEC5A表达与TTN和CDK12突变显著相关，并影响肿瘤进展和免疫相关基因的拷贝数。对OC微环境中免疫特征及风险模型的研究可揭示影响预后的因素并指导临床分层治疗。CLEC5A可作为影响OC免疫微环境重塑的潜在关键基因，为提高OC免疫治疗效果提供新视角。
Zotero 插件
