Cuproptosis-Related lncRNA Gene Signature Establishes a Prognostic Model of Gastric Adenocarcinoma and Evaluate the Effect of Antineoplastic Drugs

Abstract

Background: One of the most frequent malignancies of the digestive system is stomach adenocarcinoma (STAD). Recent research has demonstrated how cuproptosis (copper-dependent cell death) differs from other cell death mechanisms that were previously understood. Cuproptosis regulation in tumor cells could be a brand-new treatment strategy. Our goal was to create a cuproptosis-related lncRNA signature. Additionally, in order to evaluate the possible immunotherapeutic advantages and drug sensitivity, we attempted to study the association between these lncRNAs and the tumor immune microenvironment of STAD tumors. Methods: The TCGA database was accessed to download the RNA sequencing data, genetic mutations, and clinical profiles for TCGA STAD. To locate lncRNAs related to cuproptosis and build risk-prognosis models, three techniques were used: co-expression network analysis, Cox-regression techniques, and LASSO techniques. Additionally, an integrated methodology was used to validate the models’ predictive capabilities. Then, using GO and KEGG analysis, we discovered the variations in biological functions between each group. The link between the risk score and various medications for STAD treatment was estimated using the tumor mutational load (TMB) and tumor immune dysfunction and rejection (TIDE) scores. Result: We gathered 22 genes linked to cuproptosis based on the prior literature. Six lncRNAs related to cuproptosis were used to create a prognostic marker (AC016394.2, AC023511.1, AC147067.2, AL590705.3, HAGLR, and LINC01094). After that, the patients were split into high-risk and low-risk groups. A statistically significant difference in overall survival between the two groups was visible in the survival curves. The risk score was demonstrated to be an independent factor affecting the prognosis by both univariate and multivariate Cox regression analysis. Different risk scores were substantially related to the various immunological states of STAD patients, as further evidenced by immune cell infiltration and ssGSEA analysis. The two groups had differing burdens of tumor mutations. In addition, immunotherapy was more effective for STAD patients in the high-risk group than in the low-risk group, and risk scores for STAD were substantially connected with medication sensitivity. Conclusions: We discovered a marker for six cuproptosis-associated lncRNAs linked to STAD as prognostic predictors, which may be useful biomarkers for risk stratification, evaluation of possible immunotherapy, and assessment of treatment sensitivity for STAD.

A novel disulfidptosis-related lncRNA signature for predicting prognosis and potential targeted therapy in hepatocellular carcinoma

“…AL590705.3 has been confirmed to serve as a prognostic predictor in multiple tumor types, including gastric cancer and HCC. [35,36] Previous bioinformatics analysis have also demonstrated the potential of AL590705.3 as a prognostic biomarker or therapeutic target. [37,38] Previous studies [39][40][41][42] have used AC026412.3 in the development of multiple prognostic models of HCC with satisfactory performance.…”

Identification of cuproptosis hub genes contributing to the immune microenvironment in ulcerative colitis using bioinformatic analysis and experimental verification

“…Studies have shown that cuproptosis is closely related to the prognosis of pan-cancers, activation/inhibition of cancer signature pathways, and regulation of the tumor microenvironment ( 51 ). Moreover, the prognostic risk model established by cuproptosis-related lncRNAs has been shown in gastric adenocarcinoma ( 52 ), hepatocellular carcinoma ( 53 ), non-small cell lung cancer ( 54 ), and colorectal cancer ( 55 ), all of which provide a certain basis for individual prognosis and drug efficacy. Similarly, risk models constructed by cuproptosis-related miRNA also play a role in the prediction and treatment of hepatocellular carcinoma ( 56 ).…”

Causal associations of hyperthyroidism with prostate cancer, colon cancer, and leukemia: a Mendelian randomization study

“…Furthermore, recent research had also identified cuproptosis, a copper-dependent regulated cell death mechanism, as a potentially new treatment strategy for cancer. A lncRNA signature linked to cuproptosis was found to be associated with prognostic predictors for stomach adenocarcinoma (STAD), indicating its potential as a biomarker for risk stratification, evaluation of possible immunotherapy, and assessment of treatment sensitivity for STAD ( 25 , 26 ). Although thyroid hormones played an important role in the processes related to cancer occurrence and progression, their mechanisms were complex and multifaceted.…”