An immune-related pseudogene signature to improve prognosis prediction of endometrial carcinoma patients

Shanshan Tang,Yiyi Zhuge

doi:10.1186/s12938-021-00902-7

Abstract

BackgroundPseudogenes show multiple functions in various cancer types, and immunotherapy is a promising cancer treatment. Therefore, this study aims to identify immune-related pseudogene signature in endometrial cancer (EC).MethodsGene transcriptome data of EC tissues and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) through UCSC Xena browser. Spearman correlation analysis was performed to identify immune-related pseudogenes (IRPs) between the immune genes and pseudogenes. Univariate Cox regression, LASSO, and multivariate were performed to develop a risk score signature to investigate the different overall survival (OS) between high- and low-risk groups. The prognostic significance of the signature was assessed by the Kaplan–Meier curve, time-dependent receiver operating characteristic (ROC) curve. The abundance of 22 immune cell subtypes of EC patients was evaluated using CIBERSORT.ResultsNine IRPs were used to build a prognostic signature. Survival analysis revealed that patients in the low-risk group presented longer OS than those in the high-risk group as well as in multiple subgroups. The signature risk score was independent of other clinical covariates and was associated with several clinicopathological variables. The prognostic signature reflected infiltration by multiple types of immune cells and revealed the immunotherapy response of patients with anti-programmed death-1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) therapy. Function enrichment analysis revealed that the nine IRPs were mainly involved in multiple cancer-related pathways.ConclusionWe identified an immune-related pseudogene signature that was strongly correlated with the prognosis and immune response to EC. The signature might have important implications for improving the clinical survival of EC patients and provide new strategies for cancer treatment.

Highlights

Pseudogenes show multiple functions in various cancer types, and immunotherapy is a promising cancer treatment
We investigated the prognostic value of this signature in various clinical groups and the potential role of the immunerelated pseudogenes signature in immune checkpoint inhibitors immunotherapy, with the aim of using it as a promising immune therapeutic target
In conclusion, we proposed an immune-related pseudogenes signature, which can be used as an independent prognostic biomarker in stratifying risk subgroups in terms of overall survival (OS) for patients with endometrial cancer (EC)

Summary

Introduction

Pseudogenes show multiple functions in various cancer types, and immunotherapy is a promising cancer treatment. Earlystage patients presented a favorable clinical outcome with a 5-year survival rate of 95%. Patients in advanced stage had a reduced 5-year survival rate of lower than 20% for stage IV [3]. Adjuvant chemotherapy, radiation, immunotherapy, and hormonal therapy are common models of treatment for patients with EC and have reduced the mortality of patients to a certain extent in recent years. Despite rapid advances in the treatments of UCEC, the incidence and mortality rates are still increasing since it is a clinically heterogeneous disease characterized by different genetic background and pathogenesis [4]. To improve the survival rates of UCEC patients, it is imperative to identify mechanistic differences at the molecular level and develop novel predictive biomarkers to predict patient outcomes accurately

Objectives

Methods

Results

Discussion

Conclusion