AUTHOR=Chen Xi , Hu Gang , Xiong Li , Xu Qingqing 

TITLE=Relationships of Cuproptosis-Related Genes With Clinical Outcomes and the Tumour Immune Microenvironment in Hepatocellular Carcinoma

JOURNAL=Pathology and Oncology Research

VOLUME=Volume 28 - 2022

YEAR=2022

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2022.1610558

DOI=10.3389/pore.2022.1610558

ISSN=1532-2807

ABSTRACT=Background: Cuproptosis is a recently identified form of regulated cell death that plays a critical role in the onset and progression of various cancers. However, the effects of cuproptosis-related genes (CRGs) on hepatocellular carcinoma (HCC) have been poorly understood. We aimed to identify cuproptosis subtypes and develop a novel prognostic model in HCC.
Methods: We collected gene expression data and clinical outcomes from TCGA, ICGC, and GEO datasets, analyzed and identified 16 CRGs and differnet subtypes of cuproptosis related to overall survival (OS), and further examined the differences in prognosis and immune infiltration between the two subtypes. With the aid of cuproptosis subtypes, significantly differentially expressed genes (DEGs) were screened to generate a novel prognostic model. The relationship of signature with the immune landscape as well as the sensitivity of different therapies was explored. Moreover, the nomogram was performed to predict prognosis at different clinicopathological characteristics.
Results: Three cuproptosis subtypes were identified on basis of 16 CRGs and found subtype B had advanced clinical stage and worse OS. The immune response and function of the cluster B were significantly suppressed, which may be an important reason for their poor prognosis. A prognostic model of five CRGs was constructed on basis of DEGs between the three subtypes and its effectiveness was verified using two external validation sets. Moreover, after combining the risk score and clinical characteristics, a nomogram was constructed to evaluate the prognosis for HCC patients. Low- and high-risk patients exhibit distinct immune cell infiltration and immune checkpoint changes. By further analyzing the risk score, patients in the high-risk group were resistant to immunotherapy and a variety of chemotherapy drugs.
Conclusions: Our study identified the cuproptosis subtypes and established a novel prognostic model to improve the prognosis prediction and targeted therapy for HCC patients.