Mining TCGA Data for Key Biomarkers Related to Immune Microenvironment in Endometrial cancer by Immune Score and Weighted Correlation Network Analysis.

Chengbin Guo,Yuqin Tang,Gen Li,Yongqiang Zhang

doi:10.3389/fmolb.2021.645388

Abstract

Background: Endometrial cancer (EC) is one of the most lethal gynecological cancers around the world. The aim of this study is to identify the potential immune microenvironment-related biomarkers associated with the prognosis for EC. Methods: RNA-seq data and clinical information of EC patients were derived from The Cancer Genome Atlas (TCGA). The immune score of each EC sample was obtained by ESTIMATE algorithm. Weighted gene co-expression network analysis (WGCNA) was used to identify the interesting module and potential key genes concerning the immune score. The expression patterns of the key genes were then verified via the GEPIA database. Finally, CIBERSORT was applied to evaluate the relative abundances of 22 immune cell types in EC. Results: Immune scores were significantly associated with tumor grade and histology of EC, and high immune scores may exert a protective influence on the survival outcome for EC. WGCNA indicated that the black module was significantly correlated with the immune score. Function analysis revealed it mainly involved in those terms related to immune regulation and inflammatory response. Moreover, 11 key genes (APOL3, C10orf54, CLEC2B, GIMAP1, GIMAP4, GIMAP6, GIMAP7, GIMAP8, GYPC, IFFO1, TAGAP) were identified from the black module, validated by the GEPIA database, and revealed strong correlations with infiltration levels of multiple immune cell types, as was the prognosis of EC. Conclusion: In this study, 11 key genes showed abnormal expressions and strong correlations with immune infiltration in EC, most of which were significantly associated with the prognosis of EC. These findings made them promising therapeutic targets for the treatment of EC.

Highlights

Endometrial cancer (EC) is one of the most common gynecologic malignancies and represents the leading cause of morbidity and mortality among women worldwide (Ventriglia et al, 2017)
EC is histologically classified into several subtypes, including endometrioid endometrial adenocarcinoma (EEC), serous endometrial adenocarcinoma (ESC), mixed serous and endometrioid (MSE), clear cell, and malignant mixed Mullerian tumors (MMMT) (Gaber et al, 2016; Urick and Bell, 2019)
To investigate the relevance to clinical variables, 545 EC patients were classified by grade, histology, stage, age, height, weight, BMI, and tumor burden

Summary

Introduction

Endometrial cancer (EC) is one of the most common gynecologic malignancies and represents the leading cause of morbidity and mortality among women worldwide (Ventriglia et al, 2017). In 2020, it occurred 65,620 new cases and caused 12,590 deaths in the United States (Siegel et al, 2020). EC is histologically classified into several subtypes, including endometrioid endometrial adenocarcinoma (EEC), serous endometrial adenocarcinoma (ESC), mixed serous and endometrioid (MSE), clear cell, and malignant mixed Mullerian tumors (MMMT) (Gaber et al, 2016; Urick and Bell, 2019). EEC is the most common histology, representing about 75% of all endometrial cancers, followed by ESC (1–5%) and clear cell (1–5%) (Murali et al, 2014).

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