Pyroptosis-related lncRNAs are potential biomarkers for predicting prognoses and immune responses in patients with UCEC

Mol Ther Nucleic Acids. 2022 Jan 25:27:1036-1055. doi: 10.1016/j.omtn.2022.01.018. eCollection 2022 Mar 8.

Abstract

Uterine corpus endometrial carcinoma (UCEC) is a malignant disease globally, and there is no unified prognostic signature at present. In our study, two clusters were identified. Cluster 1 showed better prognosis and higher infiltration level, such as tumor microenvironment (TME), tumor mutation burden (TMB), and immune checkpoint genes expression. Gene set enrichment analysis (GSEA) indicated that some tumor-related pathways and immune-associated pathways were exposed. What is more, six pyroptosis-related long noncoding RNAs (lncRNAs) (PRLs) were applied to establish a prognostic signature through multiple Cox regression analysis. In both training and testing sets, patients with higher risk score had poorer survival than patients with low risk. The area under the curve (AUC) of receiver operating characteristic (ROC) curves performed that the survival probability was better in people with lower risk score. Mechanism analysis revealed that high risk score was correlated with reduced immune infiltration and T cells exhaustion, matching the definition of an "immune-desert" phenotype. Patients with lower risk score were characterized by higher immune checkpoint gene expression and TMB and have a sensitive response to immunotherapy and chemotherapy compared with patients with high risk score. The signature has accurate prediction ability of UCEC and is a promising therapeutic target to improve the effect of immunotherapy.

Keywords: TME; UCEC; immunotherapy; lncRNAs; prognostic signature; pyroptosis; tumor microenvironment.