Huo Xiao, Yang Mo, Zhang Xi, Wang Shuzhen, Sun Hengzi
Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China.
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
J Oncol. 2022 Aug 30;2022:7745675. doi: 10.1155/2022/7745675. eCollection 2022.
Tumor microenvironment (TME) is the crucial mediator of tumor progression, and the TME model based on immune cell infiltration to characterize ovarian cancer is considered to be a promising strategy.
Sample data of three ovarian cancer cohorts were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The scores of 22 kinds of immune cells were calculated based on CIBERSORT, and the TME clusters (TMECs) of ovarian cancer was determined by ConsensusClusterPlus. Genomic subtype was identified by non-negative matrix factorization (NMF). A TME scoring scheme was constructed using -means algorithm and principal component analysis (PCA) to quantify the TME infiltration pattern of individuals.
Four TME subtypes of ovarian cancer samples were defined: TMEC1, TMEC2, TMEC3, and TMEC4. There were also significant differences in overall survival (OS) among the four TMEC, and the OS of TMEC3 was the longest. The difference analysis of TMEC3 and the other three TMECs respectively identified the DEGs and took the intersection, and 585 DEGs were obtained. Two genomic subtypes were identified by NMF based on the expression of 585 genes, which were called GeneC1 and GeneC2. The TME scoring scheme constructed by -means and PCA algorithm was used to calculate the TME score of ovarian cancer in TCGA. High-TME score was significantly correlated with shorter survival time, older age, lower immunoactivated molecules, and immune checkpoint gene expression.
This study highlighted the complexity and diversity of TME infiltration patterns in ovarian cancer and constructed a set of TME scoring scheme to reveal TME infiltration patterns and provided new insights into the landscape of TME.
肿瘤微环境(TME)是肿瘤进展的关键介质,基于免疫细胞浸润来表征卵巢癌的TME模型被认为是一种有前景的策略。
从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)获取三个卵巢癌队列的样本数据。基于CIBERSORT计算22种免疫细胞的分数,并通过ConsensusClusterPlus确定卵巢癌的TME簇(TMECs)。通过非负矩阵分解(NMF)鉴定基因组亚型。使用均值算法和主成分分析(PCA)构建TME评分方案,以量化个体的TME浸润模式。
定义了卵巢癌样本的四种TME亚型:TMEC1、TMEC2、TMEC3和TMEC4。这四种TMEC的总生存期(OS)也存在显著差异,TMEC3的OS最长。分别对TMEC3与其他三种TMEC进行差异分析,鉴定出差异表达基因(DEGs)并取交集,共获得585个DEGs。基于585个基因的表达,通过NMF鉴定出两种基因组亚型,分别称为GeneC1和GeneC2。使用均值和PCA算法构建的TME评分方案计算了TCGA中卵巢癌的TME评分。高TME评分与较短的生存时间、较高的年龄、较低的免疫激活分子以及免疫检查点基因表达显著相关。
本研究突出了卵巢癌中TME浸润模式的复杂性和多样性,并构建了一套TME评分方案以揭示TME浸润模式,为TME格局提供了新的见解。