Identification and validation of a novel cuproptosis-related genes signature associated with prognosis, clinical implications and immunotherapy of hepatocellular carcinoma

Abstract

Background: Cuproptosis is a novel type of regulated cell death and is reported to promote tumor occurrence and progression. However, whether a cuproptosis-related signature has an impact on hepatocellular carcinoma (HCC) is still unclear.Materials and methods: We analyzed the transcriptome data of HCC from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database, and searched for tumor types with different cuproptosis patterns through consistent clustering of cuproptosis genes. We then constructed a Cuproptosis-Related Genes (CRGs)-based risk signature through LASSO COX regression, and further analyzed its impact on the prognosis, clinical characteristics, immune cell infiltration, and drug sensitivity of HCC.Results: We identified the expression changes of 10 cuproptosis-related genes in HCC, and all the patients can be divided into two subtypes with different prognosis by applying the consensus clustering algorithm. We then constructed a cuproptosis-related risk signature and identified five CRGs, which were highly correlated with prognosis and representative of this gene set, namely G6PD, PRR11, KIF20A, EZH2, and CDCA8. Patients in the low CRGs signature group had a favorable prognosis. We further validated the CRGs signature in ICGC cohorts and got consistent results. Besides, we also discovered that the CRGs signature was significantly associated with a variety of clinical characteristics, different immune landscapes and drug sensitivity. Moreover, we explored that the high CRGs signature group was more sensitive to immunotherapy.Conclusion: Our integrative analysis demonstrated the potential molecular signature and clinical applications of CRGs in HCC. The model based on CRGs can precisely predict the survival outcomes of HCC, and help better guide risk stratification and treatment strategy for HCC patients.

Prognosis and chemotherapy drug sensitivity in liver hepatocellular carcinoma through a disulfidptosis-related lncRNA signature

“…Therefore, targeted therapy and immunotherapy had become increasingly important with the development of molecular biology. In recent years, several prognostic models based on autophagy-related genes 21 , ferroptosis-related genes 22 , cuproptosis-related genes 23 , pyroptosis-related genes 24 have been constructed to predict the prognosis of different cancers. Not only mRNAs but also lncRNAs had been used to establish prognostic models for predicting prognosis 25 – 28 .…”

Immunomodulation of cuproptosis and ferroptosis in liver cancer

“…CAF is abundant in TME. In the process of liver cancer, along with the aggregation of CAF, CAF interacts with TME immune infiltrating cells through effector molecules, which can transform TME into an immunosuppressive type, help tumor cells evade immune surveillance, and carry out immune escape, indicating CAF provides an immune microenvironment for liver cancer that is conducive to its proliferation and metastasis [ 11 , 70 , 71 ]. Several long noncoding RNAs (lncRNAs) have been found to shape the tumor microenvironment through epigenetic regulation in tumor cells [ 72 ].…”