Identification of a 3-cuproptosis-associated-lncRNA-signature that predicts the prognosis of endometrial cancer patients

Abstract

Endometrial carcinoma is a common malignancy among peri-menopausal and menopausal females, even among some women of reproductive age. The treatment approach to endometrial cancer is a platinum-based regimen combined with paclitaxel, which may be unsatisfactory. A copper-mediated binding of lipoylated constituents of tricarboxylic acid cycle has been found recently, which brings about lethal protein stress and cell death, a phenomenon termed cuproptosis. As an innovative method of cell death, cuproptosis could be designed for cancer treatment and many aspects remain unaddressed. In our study, clinical, genomic, and mutational profiles of uterine corpus endometrial carcinoma (UCEC) patients were obtained from The Cancer Genome Atlas and cuproptosis-related genes and long non-coding RNAs (lncRNAs) were acquired thereafter. Co-expression and Cox regression analyses led to the development of a prognostic signature. Patients were separated into two groups (high- and low-risk groups) and survival analysis, risk score calculation, multivariate Cox analysis, and subgroup validation were implemented to determine the utility of the signature. Differentially expressed genes (DEGs) between the two groups were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Immune-related functional analysis and tumor mutation burden (TMB) analysis were performed. Three independent high-risk cuproptosis-related lncRNAs were finally confirmed and incorporated into the prognostic model, including BX322234.1, LINC01545 and LINC01224. Areas under the curve for 1-, 3- and 5-year survival were 0.717, 0.688 and 0.714, respectively. The risk model served as an independent factor to predict prognosis. Patients with high-risk and low TMB tended to have poor prognoses. Enrichment analysis demonstrated that DEGs were mostly associated with immune responses. In conclusion, the three high-risk cuproptosis-related lncRNAs could predict the prognosis of UCEC patients with higher power, where patients with high-risk and low TMB are prone to have the worst prognosis, which broadens the pattern of clinical treatment and applications.