Abstract
Extensive evidence has revealed that ferroptosis plays a vital role in HCC development and progression. Fanconi anemia complementation group D2 (FANCD2) has been reported to serve as a ferroptosis-associated gene and has a close relationship with tumorigenesis and drug resistance. However, the impact of the FANCD2-related immune response and its mechanisms in HCC remains incompletely understood. In the current research, we evaluated the prognostic significance and immune-associated mechanism of FANCD2 based on multiple bioinformatics methods and databases. The results demonstrated that FANCD2 was commonly upregulated in 15/33 tumors, and only the high expression of FANCD2 in HCC was closely correlated with worse clinical outcomes by OS and DFS analyses. Moreover, ncRNAs, including two major types, miRNAs and lncRNAs, were closely involved in mediating FANCD2 upregulation in HCC and were established in a ceRNA network by performing various in silico analyses. The DUXAP8-miR-29c-FANCD2 and LINC00511-miR-29c-FANCD2 axes were identified as the most likely ncRNA-associated upstream regulatory axis of FANCD2 in HCC. Finally, FANCD2 expression was confirmed to be positively related to HCC immune cell infiltration, immune checkpoints, and IPS analysis, and GSEA results also revealed that this ferroptosis-associated gene was primarily involved in cancer-associated pathways in HCC. In conclusion, our investigations indicate that ncRNA-related modulatory overexpression of FANCD2 might act as a promising prognostic and immunotherapeutic target against HCC.