Development and Verification of a Newly Established Cuproptosis-associated LncRNA Model for Predicting Overall Survival in Uterine Corpus Endometrial Carcinoma

Background: Uterine corpus endometrial carcinoma (UCEC) is a prevalent gynecologic malignant tumor with high recurrence and mortality rates. This study aimed to develop and validate a prognostic model for patients with UCEC based on cuproptosis-related long non-coding RNA (lncRNA) signature.

Methods: Transcriptome and clinical UCEC data were obtained from The Cancer Genome Atlas (TCGA) database. Correlation analysis was conducted to screen out the cuproptosis-related lncRNAs, and univariate regression analysis was performed to determine prognostic factors associated with overall survival (OS). A cuproptosis-related lncRNA risk model was constructed through least absolute shrinkage and selection operator (LASSO) regression and cross-validation. The accuracy and reliability of the model were verified through Kaplan-Meier (KM), proportional hazards model (Cox) regression, nomogram, principal component analysis (PCA), and stage analysis. Gene Ontology (GO) enrichment, immune function, and tumor mutation burden (TMB) analyses were conducted between low-risk and high-risk groups, and antineoplastic drugs were predicted.

Results: By correlation analysis, 155 cuproptosis-related lncRNAs were acquired, and 9 lncRNAs were identified as independent prognostic factors. A 6-cuproptosis-related lncRNA model was established. The results revealed that patients in the high-risk group were more inclined to have a poor OS than those in the low-risk group. Risk score was an independent prognostic factor and had a high accuracy and predictive value. The extracellular structure and anchored components of membrane-related GO terms were significantly enriched. Immune function and TMB results were assumed to be different from each other, which might explain a better outcome in the low-risk group than that in the high-risk group. Eighteen compounds were predicted as chemotherapy drugs with high half maximal inhibitory concentration (IC50) in the high-risk group.

Conclusions: We successfully developed a cuproptosis-related lncRNA risk model for the prediction of prognosis, while simultaneously providing insights on new approaches for immunotherapy and chemotherapy for patients with UCEC.