A Novel Oncogenic Role of FDX1 in Human Melanoma Related to PD-L1 Immune Checkpoint.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37298135", "kind": "science-record", "revision": 3, "content_hash": "sha256:46ccb98714acc318515cd8fea206e259b781abc45af197df2acb79407aacb6dc", "created_at": "2026-11-01T19:02:01Z", "updated_at": "2026-11-01T22:09:39Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A Novel Oncogenic Role of FDX1 in Human Melanoma Related to PD-L1 Immune Checkpoint.", "doi": "10.3390/ijms24119182", "pmid": "37298135", "authors": ["Huijiao Lu", "Jiahua Liang", "Xue He", "Huabin Ye", "Chuangdong Ruan", "Hongwei Shao", "Rongxin Zhang", "Yan Li"], "journal": "International journal of molecular sciences", "year": 2023, "abstract": "The aim of this study was to evaluate the association between Ferredoxin 1 (FDX1) expression and the prognostic survival of tumor patients and predict the efficacy of immunotherapy response to antitumor drug sensitivity. FDX1 plays an oncogenic role in thirty-three types of tumors, based on TCGA and GEO databases, and further experimental validation in vitro was provided through multiple cell lines. FDX1 was expressed highly in multiple types of cancer and differently linked to the survival prognosis of tumorous patients. A high phosphorylation level was correlated with the FDX1 site of S177 in lung cancer. FDX1 exhibited a significant association with infiltrated cancer-associated fibroblasts and CD8+ T cells. Moreover, FDX1 demonstrated correlations with immune and molecular subtypes, as well as functional enrichments in GO/KEGG pathways. Additionally, FDX1 displayed relationships with the tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, and RNA and DNA synthesis (RNAss/DNAss) within the tumor microenvironment. Notably, FDX1 exhibited a strong connection with immune checkpoint genes in the co-expression network. The validity of these findings was further confirmed through Western blotting, RT-qPCR, and flow cytometry experiments conducted on WM115 and A375 tumor cells. Elevated FDX1 expression has been linked to the enhanced effectiveness of PD-L1 blockade immunotherapy in melanoma, as observed in the GSE22155 and GSE172320 cohorts. Autodocking simulations have suggested that FDX1 may influence drug resistance by affecting the binding sites of antitumor drugs. Collectively, these findings propose that FDX1 could serve as a novel and valuable biomarker and represent an immunotherapeutic target for augmenting immune responses in various human cancers when used in combination with immune checkpoint inhibitors.", "claims": [{"id": "claim-method", "statement": "Statistically significant p-value calculated (Pearson correlation analysis): * p < 0.05, ** p < 0.01, *** p < 0.001.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37298135", "locator": "sections[8] \"2.6. 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In order to", "SKCM cancer showed high FDX1 expression via Western blotting (Beyotime, Shanghai, China) and RT-qPCR (Nov", "KCM tumors by WM115 and A375 cell lines. (A) Western blotting examination of the protein levels of WM115 a"], "order_basis": "paper_text_order:1266", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["further confirmed through Western blotting, RT-qPCR, and flow cytometry experiments conducted on", "rther confirmed through Western blotting, RT-qPCR, and flow cytometry experiments conducted on", "g knockdown of FDX1 using techniques such as RT-qPCR, Western blotting (WB), and flow cytometry (", "ern blotting (Beyotime, Shanghai, China) and RT-qPCR (Novoprotein, Shanghai, China) (Figure 6A,B)"], "order_basis": "paper_text_order:1285", "id": "assay:2"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["irmed through Western blotting, RT-qPCR, and flow cytometry experiments conducted on WM115 and A375 tumo", "such as RT-qPCR, Western blotting (WB), and flow cytometry (FCM). 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FDX1 knockdown impacts PD-L1 expression in SKCM tumors by W"], "order_basis": "paper_text_order:3241", "id": "assay:4"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["1 expression in healthy and tumor tissues by immunohistochemistry based on the HPA database (Figure 6D). All a", "acent normal tissues of SKCM was analyzed by immunohistochemistry based on HPA dataset (IHC staining: 100 μm).", "y immunohistochemistry based on HPA dataset (IHC staining: 100 μm). 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