Identification and Validation of Novel Immunogenic Cell Death- and DNA Damage Response-Related Molecular Patterns Correlated with Immune Status and Prognosis in Hepatocellular Carcinoma

Abstract

Immunogenic cell death (ICD) and DNA damage response (DDR) are involved in cancer progression and prognosis. Currently, chemotherapy is the first-line treatment for intermediate or advanced hepatocellular carcinoma (HCC), which is mostly based on platinum and anthracyclines that induce DNA damage and ICD. With the treatment of HCC with immune checkpoint inhibitors (ICIs), it is important to understand the molecular characteristics and prognostic values of ICD and DDR-related genes (IDRGs). We aimed to explore the characteristics of ICD and DDR-related molecular patterns, immune status, and the association of immunotherapy and prognosis with IDRGs in HCC. We identified IDRGs in HCC and evaluated their differential expression, biological behaviors, molecular characteristics, immune cell infiltration, and prognostic value. Prognostic IDRGs and subtypes were identified and validated. FFAR3, DDX1, POLR3G, FANCL, ADA, PI3KR1, DHX58, TPT1, MGMT, SLAMF6, and EIF2AK4 were determined as risk factors for HCC, and the biological experiments indicated that high FANCL expression is harmful to the treatment and prognosis. HCC was classified into high- and low-risk groups based on the median values of the risk factors to construct a predictive nomogram. These findings provide novel insights into the treatment and prognosis of HCC and provide a new research direction for HCC.

Keywords

• Hepatocellular carcinoma
• Immunogenic cell death
• DNA damage response
• Immunotherapy
• Prognosis