The Cuproptosis-Related Long Noncoding RNA Signature Predicts Prognosis and Immune Cell Infiltration in Hepatocellular Carcinoma

Abstract

Background. Hepatocellular carcinoma (HCC), ranking as one of the most common malignant tumors, is one of the leading causes of cancer death, with a poor prognosis. Cuproptosis, a novel programmed cell death modality that has just been confirmed recently, may play an important role in HCC prognosis. Long noncoding RNA (LncRNA) is a key participant in tumorigenesis and immune responses. It may be of great significance to predict HCC based on cuproptosis genes and their related LncRNA. Methods. The sample data on HCC patients were obtained from The Cancer Genome Atlas (TCGA) database. Combined with cuproptosis-related genes collected from the literature search, expression analysis was carried out to find cuproptosis genes and their related LncRNAs significantly expressed in HCC. The prognostic model was constructed by least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression. The feasibility of these signature LncRNAs used for the evaluation of the overall survival rate in HCC patients as independent factors was investigated. The expression profile of cuproptosis, immune cell infiltration, and the status of somatic mutation were analyzed and compared. Results. A prognostic model of HCC consisting of seven cuproptosis gene-related LncRNA signatures was constructed. Multiple verification methods have showed that this model can accurately predict the prognosis of HCC patients. It was showed that the classified high-risk group under the risk score of this model had worse survival status, more significant expression of the immune function, and higher mutation frequency. During the analysis, the cuproptosis gene CDKN2A was found to be most closely related to LncRNA DDX11-AS1 in the expression profile of HCC patients. Conclusion. The cuproptosis-related signature LncRNA in HCC was identified, on the basis of which a model was constructed, and it was verified that it can be used to predict the prognosis of HCC patients. The potential role of these cuproptosis-related signature LncRNAs as new targets for disease therapy in antagonizing HCC development was discussed.

Anoikis-related lncRNA signature predicts prognosis and is associated with immune infiltration in hepatocellular carcinoma

“…Several studies have developed candidate lncRNA models for apoptosis-related pathways of HCC. DDX11-AS1 is used in prognosis models related to ferroptosis, cuproptosis, and cancer cell stemness [21][22][23]. AL031985.3 is associated with liver cancer ferroptosis, cuproptosis, pyroptosis, and autophagy-related prognosis models [24][25][26], while AC026412.3 is included in the model predicting copper mortality and focal mortality in HCC [27,28].…”

Anoikis-Related LncRNA Signature Predicts Prognosis and Is Associated With Immune Infiltration in Hepatocellular Carcinoma

“…Several studies have developed candidate lncRNA models for apoptosis-related pathways of hepatocellular carcinoma, with DDX11-AS1 used in prognosis models related to ferroptosis, cuproptosis, and cancer cell stemness [25][26][27]. AL031985.3 is associated with liver cancer ferroptosis, cuproptosis, pyroptosis, and autophagy-related prognosis models[28-30], while AC026412.3 is included in the model predicting copper mortality and focal mortality in hepatocellular carcinoma [31,32].…”

Copper in colorectal cancer: From copper‐related mechanisms to clinical cancer therapies

“…By constructing a prognostic risk model utilising copper‐associated long noncoding RNAs (lncRNAs; CRLncSig), it was uncovered that the low‐risk group demonstrated prolonged overall survival (OS) in comparison to the high‐risk group. Additionally, the low‐risk group exhibited decreased tumour purity, enhanced immune cell infiltration, elevated immune scores, enriched immune activation pathways, and a more favourable response to immunotherapy 147 . The role of cuproptosis in CRC immunotherapy has primarily focused on FDX1 and DLAT.…”