Comprehensive Analysis of the Glycolysis-Related Gene Prognostic Signature and Immune Infiltration in Endometrial Cancer.

Xiao Yang,Yuan Cheng,Lijun Zhao,Boqiang Shen,Xingchen Li,Jingyi Zhou,Jianliu Wang

doi:10.3389/fcell.2021.797826

Abstract

Glucose metabolic reprogramming and immune imbalance play important roles in the progression of cancers. The purpose of this study is to develop a glycolysis-related prognostic signature for endometrial cancer (EC) and analyze its relationship with immune function. The mRNA expression profiling of the glycolysis-related genes and clinical data of EC patients were downloaded from The Cancer Genome Atlas (TCGA). We identified a glycolysis-related gene prognostic signature for predicting the prognosis of EC by using The Least Absolute Shrinkage and Selection Operator (LASSO) regression and found the patients in the high-risk group had worse survival prognosis. Multivariate Cox regression analysis showed that the gene signature was an independent prognostic factor for EC. The ROC curve confirmed the accuracy of the prognostic signature (AUC = 0.730). Then, we constructed a nomogram to predict the 1–5 years survival rate of EC patients. The association between the gene signature and immune function was analyzed based on the “ESTIMATE” and “CIBERSORT” algorithm, which showed the immune and ESTIMATE scores of patients in the high-risk group were lower, while the low immune and ESTIMATE scores were associated with a worse prognosis of patients. The imbalance of immune cells was also found in the high-risk group. Further, the protein of CDK1, a gene in the signature, was found to be closely related to prognosis of EC and inhibition of CDK1 could inhibit migration and promote apoptosis of EC cells. This study reveals a link between glycolysis-related gene signature and immunity, and provides personalized therapeutic targets for EC.

Highlights

Endometrial cancer (EC) is one of the most common gynecological malignancies
Metastasis with the smallest number of immune cells entering represented the worst immune microenvironment, and immune escape was most likely to occur under this condition (Van den Eynde et al, 2018). These results suggested that the poor prognosis of patients in the high-risk subgroup might be closely related to the low immune scores
We identified a glycolysis-related 10 gene signature for predicting the prognosis of EC patients based on The Cancer Genome Atlas (TCGA), where higher risk scores represent a worse prognosis

Summary

Introduction

Endometrial cancer (EC) is one of the most common gynecological malignancies. The latest cancer statistics of the American Cancer Society showed that the number of new cases in the United States increased by 63,230, with 11,350 deaths being reported, and the incidence rate ranked fourth in female malignant tumors and sixth in deaths in 2018 (Sheikh et al, 2014; Siegel et al, 2018). It is urgent to explore new prognostic biomarkers and therapeutic targets. Metabolic reprogramming is one of the most important characteristics of tumor cells. Studies have shown that the glucose metabolism reprogramming of tumor cells is closely related to the occurrence, progression, and chemotherapy resistance of tumors (Icard et al, 2018). It was reported that multiple genes could promote the progression of EC by promoting glycolysis (Han et al, 2019). Since glucose metabolism reprogramming is an important feature that distinguishes tumor cells from normal cells, it may be of great significance to explore prognostic genes and potential therapeutic targets of EC from the perspective of abnormal glucose metabolism

Objectives

Methods

Results

Discussion

Conclusion