Construction of an endoplasmic reticulum stress and cuproptosis -related lncRNAs signature in chemosensitivity in hepatocellular carcinoma by comprehensive bioinformatics analysis

Abstract

Endoplasmic reticulum stress (ERS) and cuproptosis have remarkable effects on hepatocellular carcinoma (HCC) leading to a poor prognosis. The current study aimed to explore credible signature for predicting the prognosis of HCC based on ERS and cuproptosis-related lncRNAs. In our study, clinical and transcriptomic profiles of HCC patients were obtained from the Cancer Genome Atlas (TCGA) database. An ERS and cuproptosis-related lncRNA prognostic signature, including NRAV, SNHG3, LINC00839 and AC004687.1, was determined by correlation tests, Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) methods. Survival and predictive value were evaluated using Kaplan–Meier and receiver operating characteristic (ROC) curves, while calibration and nomograms curves were developed. Besides the enrichment analyses for ERS and cuproptosis-related lncRNAs, mutational status and immune status were assessed with TMB and ESTIMATE. Additionally, consensus cluster analysis was employed to compare cancer subtype differences, while drug sensitivity and immunologic efficacy were evaluated for further exploration. qRT-PCR and CCK-8 were utilized to verify the alteration of the prognostic lncRNAs expression and proliferation in vitro. High-risk groups exhibited poorer prognosis. The signature exhibited robust predictive value as an independent prognostic indicator and showed significant correlation with clinicopathological features. In the enriched analysis, biological membrane pathways were enriched. Low-risk patients had lower TMB and higher immune status. A cluster analysis revealed that cluster 2 had the best clinical immunological efficacy and most active immune function. In brief, our constructed signature with ERS and cuproptosis-related lncRNAs was associated survival outcomes of HCC, and can be used to predict the clinical classification and curative effect.

Keywords

• Hepatocellular carcinoma
• Endoplasmic reticulum stress
• Long non-coding RNA
• Prognostic signature
• Candidate drugs
• Tumor immune microenvironment