Abstract 725P
Background
Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Coproptosis is a newly discovered regulated cell death caused by intracellular copper-triggered aggregation of mitochondrial lipoylated proteins and the destabilization of Fe–S cluster proteins.
Methods
We analyzed the expression changes, methylation levels, mutation status and prognosis of 13 CRGs in 538 HCC samples. Liver cancer patients were divided into two CRG clusters according to the expression of CRGs. Then HCC patients were classified according to the differential genes between the two gene clusters, and the prognosis of the two gene clusters is significantly different. A cuproptosis risk model was constructed according to the 5 risk genes using the LASSO COX method. We further constructed a nomogram to improve the clinical applicability of the risk model.
Results
The results suggested that the differences in the expression levels of CRGs in HCC may be regulated by methylation. Gsva enrichment analysis shown that CRG clusters and gene clusters were significantly enriched in the multiple tumors related signaling pathways and tumor metabolism related pathways, including TCA cycle. The relationship between CRGs, risk genes and immune microenvironment was analyzed by using CIBERSORT algorithm and single-cell data analysis method. Cuproptosis risk score was positively correlated with activated memory CD4 + T cells and negatively correlated with activated NK cells, resting memory CD4+ T cells, T regulatory cells. Finally, we conducted antineoplastic drug sensitivity analysis and provide anti-tumor treatment strategies for liver cancer patients in different subtypes. we found that Doxorubicin, Vinorelbine, and Cisplatin had lower IC50 values for patients in the high cuproptosis risk score group, while chemotherapy drugs such as Elesclomol, Gefitinib and Imatinib had lower IC50 values for patients with low cuproptosis risk score. These results suggested that cuproptosis risk model may aid in strategies for selecting anticancer drugs for HCC patients.
Conclusions
These findings may improve our understanding of CRG in HCC and provide new insights for assessing prognosis and developing more effective treatment strategies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Department of Hepatic Surgery, Fudan University Shanghai Cancer Center.
Funding
This study was supported by grants from the Clinical Research Plan of SHDC (SHDC2020CR4018), the National Natural Science Foundation of China (81902907 and 81874182) and Shanghai Pujiang Program (2019PJD008).
Disclosure
All authors have declared no conflicts of interest.