CDKN2B-AS1 Promotes Malignancy as a Novel Prognosis-Related Molecular Marker in the Endometrial Cancer Immune Microenvironment.

Di Yang,Xiao-Xin Ma,Jian Ma

doi:10.3389/fcell.2021.721676

Abstract

The prognosis of patients with endometrial cancer (EC) is closely associated with immune cell infiltration. Although abnormal long non-coding RNA (lncRNA) expression is also linked to poor prognosis in patients with EC, the function and action mechanism of immune infiltration-related lncRNAs underlying the occurrence and development of EC remains unclear. In this study, we analyzed lncRNA expression using The Cancer Genome Atlas and clinical data and identified six lncRNAs as prognostic markers for EC, all of which are associated with the infiltration of immune cell subtypes, as illustrated by ImmLnc database and ssGSEA analysis. Real-time quantitative polymerase chain reaction showed that CDKN2B-AS1 was significantly overexpressed in EC, whereas its knockdown inhibited the proliferation and invasion of EC cells and the in vivo growth of transplanted tumors in nude mice. Finally, we constructed a competing endogenous RNA regulatory network and conducted Gene Ontology enrichment analysis to elucidate the potential molecular mechanism underlying CDKN2B-AS1 function. Overall, we identified molecular targets associated with immune infiltration and prognosis and provide new insights into the development of molecular therapies and treatment strategies against EC.

Highlights

Endometrial cancer (EC) is one of the most common malignant tumors of the female reproductive system, and its incidence has increased in recent years, in younger females (Smrz et al, 2020)
Univariate Cox proportional hazard regression (PHR) analysis on the expression profiles of 340 long non-coding RNA (lncRNA) identified seven immune-related lncRNAs with p < 0.001 whose expression was related to prognosis (Figure 2A)
We explored immune-related lncRNAs in EC to improve our understanding of the mechanisms underlying EC occurrence and development, and to develop new diagnosis and therapeutic strategies, for better treatment outcomes

Summary

Introduction

Endometrial cancer (EC) is one of the most common malignant tumors of the female reproductive system, and its incidence has increased in recent years, in younger females (Smrz et al, 2020). In 2020, approximately 65,620 new cases of EC in the United States and 12,590 related deaths have been reported, with a mortality rate second only to ovarian cancer (Siegel et al, 2020). In 2013, The Cancer Genome Atlas (TCGA) had proposed a molecular typing system that divided EC into four subtypes, namely, DNA polymerase epsilon (POLE), microsatellite instability (MSI), copy number abnormalities low (CNL), and copy number abnormalities high (CNH) (Du et al, 2019). These subtypes can help to more accurately classify post-operative

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Results

Conclusion