A Newly Established Cuproptosis-Related Long Non-Coding RNA Signature for Predicting Prognosis and Immune Microenvironment in Stomach Adenocarcinoma

Abstract

Abstract Background Cuproptosis is a form of cell death that is copper-dependent and regulated. It is currently considered as a new direction for future cancer treatment. However, cuproptosis-related long noncoding RNA (LncRNA) in stomach adenocarcinoma (STAD) have few reported. Methods STAD transcriptomic data, genomic mutation data, and clinical data are downloaded from the TCGA website. First, we screened the cuproptosis-related lncRNAs and randomized STAD patients into training and validation groups. Then, cuproptosis-related lncRNA prognostic signatures were identified and a prognostic model was constructed using least absolute shrinkage selection operator Cox regression and multivariate Cox regression. We explored differences in clinical characteristics, tumor immune microenvironment, and tumor mutational burden between the two groups and assessed the ability of risk scores to predict the benefits of immunotherapy. Finally, we verified the differences in the expression of cuproptosis-related prognostic markers in gastric cancer cell lines and normal gastric epithelial cells by qRT-PCR. Results Referring to previous literature, we identified 19 cuproptosis-related genes. Through co-expression analysis, 430 cuproptosis-related lncRNAs were identified. A Cox model revealed and constructed 8 LncRNA prognostic signatures associated with cuproptosis (AC005050.3, AC016394.2, AL606970.1, BX890604.1, C5orf66, HAGLR, LINC01094, TDRKH-AS1). Based on median risk scores, STAD patients were categorized as high-risk or low-risk. Kaplan-Meier survival curves showed statistically significant differences in overall survival between the high- and low-risk groups. The receiver operating characteristic curves and principal component analysis showed that the model had better predictive ability. A nomogram of the predictive power of prognostic markers was also created using multivariate Cox regression. According to the tumor immune microenvironment, some immune cells were highly infiltrated and had a higher ESTIMATE score in the low-risk group. There was a significant difference in tumor mutation burden between groups at high and low risk. qPT-PCR results suggest that 8 LncRNA prognostic signatures are highly expressed in gastric cancer cells. Conclusion We identified eight LncRNAs associated with cuproptosis as prognostic signatures in STAD. They may be potential biological markers for predicting the prognosis of STAD patients and evaluating the effect of immunotherapy and drug sensitivity in the future.