Cuproptosis-related lncRNAs predict the clinical outcome and immune characteristics of hepatocellular carcinoma

Hongfei Zhu; Feifei Mao; Kang Wang; Jinkai Feng; Shuqun Cheng

doi:10.3389/fgene.2022.972212

Cuproptosis-related lncRNAs predict the clinical outcome and immune characteristics of hepatocellular carcinoma

Front Genet. 2022 Sep 23:13:972212. doi: 10.3389/fgene.2022.972212. eCollection 2022.

Authors

Hongfei Zhu^{1

2}, Feifei Mao¹, Kang Wang², Jinkai Feng², Shuqun Cheng^{1

2}

Affiliations

¹ Tongji University Cancer Center, Shanghai 10th People's Hospital, School of Medicine, Tongji University, Shanghai, China.
² Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

Abstract

Cuproptosis, as a novel copper-dependent and non-apoptotic form of cell death, is induced by aggregation of lipoylated mitochondrial proteins and the instability of Fe-S cluster proteins. However, the role of cuproptosis-related long noncoding RNAs (CRLncRNAs) in hepatocellular carcinoma (HCC) has not been clearly elucidated. In this study, we identified and characterized cuproptosis-related lncRNAs in HCC. 343 HCC cases from The Cancer Genome Atlas (TCGA) with gene transcriptome data and clinical data were obtained for analysis after the screening. Univariate and multivariate Cox proportional hazards analyses were performed to establish a prognostic cuproptosis-related lncRNA signature (CRlncSig). We established a prognosis-related model consisting of nine cuproptosis-related lncRNAs: GSEC, AL158166.1, AC005479.2, AL365361.1, AC026412.3, AL031985.3, LINC00426, AC009974.2, AC245060.7, which was validated in the internal cohort. High-risk group stratified by the CRlncSig was significantly related to poor prognosis (p < 0.001). The area under the receiver operating characteristic curve (AUC) of 1 year, 3 years, and 5 years of survival were 0.813, 0.789, and 0.752, respectively. Furthermore, a prognostic nomogram including CRlncSig with clinicopathologic factors was built with favorable predictive power. In addition, GO and KEGG enrichment analysis suggested that CRlncSig was involved in many carcinogenesis and immune-related pathways. Additionally, we found that tumor microenvironment, immune infiltration, immune function, and drug response were significantly different between the high-risk and low-risk groups based on the risk model. These results highlight the value of cuproptosis-related lncRNAs on prognosis for HCC patients and provide insight into molecular and immune features underlying cuproptosis-related lncRNAs, which might play an important role in patient management and immunotherapy.

Keywords: cuproptosis; hepatocellular carcinoma; immunotherapy; prognostic signature; tumor microenvironment.