Prognostic value of FDX1, the cuprotosis key gene, and its prediction models across imaging modalities and histology.

Background: Cuprotosis has been identified as a novel way of cell death. The key regulator ferredoxin 1 (FDX1) was explored via pan-cancer analysis, and its prediction models were proposed across seven malignancies and two imaging modalities.

Methods: The prognostic value of FDX1 was explored via 1654 cases of 33 types of cancer in the Cancer Genome Atlas database. The MRI cohort of hepatocellular carcinoma in the First Affiliated Hospital of Fujian Medical University, and CT and MRI images from the Cancer Imaging Archive, REMBRANDT and Duke databases were exploited to formulate radiomic models to predict FDX1 expression. After segmentation of volumes of interest and feature extraction, the recursive feature elimination algorithm was used to screen features, logistic regression was used to model features, immunohistochemistry staining with FDX1 antibody was performed to test the radiomic model.

Results: FDX1 was found to be prognostic in various types of cancer. The area under the receiver operating characteristic curve of radiomic models to predict FDX1 expression reached 0.825 (95% CI = 0.739-0.911). Cross-tissue compatibility was confirmed in pan-cancer validation and test cohorts. Mechanistically, the radiomic score was significantly correlated with various immunosuppressive genes and gene mutations. The radiomic score was also found to be an independent prognostic factor, making it a potentially actionable biomarker in the clinical setting.

Conclusions: The expression of FDX1 could be non-invasively predicted via radiomics. The radiomic patterns with biological and clinical relevance across histology and modalities could have a broad impact on a larger population of patients.