Overexpression of MTHFD2 represents an inflamed tumor microenvironment and precisely predicts the molecular subtype and immunotherapy response of bladder cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38130721", "kind": "science-record", "revision": 4, "content_hash": "sha256:49a55da4b9026daccd3804c44b12c560d04fa39512321a433da110d7665cbc0a", "created_at": "2026-11-01T19:20:03Z", "updated_at": "2026-11-01T22:53:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Overexpression of MTHFD2 represents an inflamed tumor microenvironment and precisely predicts the molecular subtype and immunotherapy response of bladder cancer.", "doi": "10.3389/fimmu.2023.1326509", "pmid": "38130721", "authors": ["Xiaokai Shi", "Xiangrong Peng", "Yin Chen", "Zebin Shi", "Chuang Yue", "Li Zuo", "Lifeng Zhang", "Shenglin Gao"], "journal": "Frontiers in immunology", "year": 2023, "abstract": "Introduction: Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), whose aberrant expression is common in cancers, has recently been identified as a potential regulator of immune response. However, its immune-related role in bladder cancer (BLCA) and its association with immunotherapy efficacy remain unclear.\nMethods: RNA sequencing data from The Cancer Genome Atlas (TCGA) was applied to analyze the immunological roles and prognostic value of MTHFD2 in pan-cancers. The association of MTHFD2 with several immunological features of tumor microenvironment (TME), including cancer-immunity cycle, immune cells infiltration, immune checkpoints expression, and T cell inflamed score was analyzed in TCGA-BLCA cohort. The predictors of cancer treatments effectiveness, including the expression and mutation of certain genes, molecular subtypes, and several signatures were evaluated as well. These results were validated by another independent cohort (GSE48075). Finally, the predictive value of MTHFD2 for TME and immunotherapy efficacy were validated using immunohistochemistry assay and RNA sequencing data from IMvigor210 cohort, respectively.\nResults: MTHFD2 was found to be positively associated with several immunological features of an inflamed tumor microenvironment (TME) in various cancers and could predict BLCA patients' prognosis. In BLCA, high expression of MTHFD2 was observed to be positively related with the cancer-immunity cycle, the infiltration of several immune cells, and the expression of immunoregulators and T-cell inflamed scores, indicating a positive correlation with the inflamed TME. Moreover, patients with high MTHFD2 expression were more likely to be basal-like subtypes and respond to BLCA treatments, including immunotherapy, chemotherapy, and target therapy. The clinical data of the IMvigor210 cohort confirmed the higher response rates and better survival benefits of immunotherapy in high-MTHFD2-expression patients.\nConclusion: Collectively, high MTHFD2 predicts an inflamed TME, a basal-like subtype, and a better response to various therapeutic strategies, especially the ICB therapy, in bladder cancer.", "claims": [{"id": "claim-method", "statement": "Wilcoxon signed rank test or Kruskal–Wallis test was applied for the differences among continuous variables according to the number of groups, and the chi-square test was applied for the differences among classified variables. The correlation analyses were based on Pearson’s coefficients. The survival of patients was compared by both univariate Cox regression and the Kaplan–Meier method.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38130721", "locator": "sections[8] \"Statistics\" paragraph 2", "quote": "Wilcoxon signed rank test or Kruskal–Wallis test was applied for the differences among continuous variables according to the number of groups, and the chi-square test was applied for the differences among classified variables. The correlation analyses were based on Pearson’s coefficients. The survival of patients was compared by both univariate Cox regression and the Kaplan–Meier method."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38130721", "locator": "sections[17] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material ."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Collectively, high MTHFD2 predicts an inflamed TME, a basal-like subtype, and a better response to various therapeutic strategies, especially the ICB therapy, in bladder cancer.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38130721", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Collectively, high MTHFD2 predicts an inflamed TME, a basal-like subtype, and a better response to various therapeutic strategies, especially the ICB therapy, in bladder cancer."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Collectively, high MTHFD2 predicts an inflamed TME, a basal-like subtype, and a better response to various therapeutic strategies, especially the ICB therapy, in bladder cancer.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38130721"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Methods: RNA sequencing data from The Cancer Genome Atlas (TCGA) was", "lidated using immunohistochemistry assay and RNA sequencing data from IMvigor210 cohort, respectively. R"], "order_basis": "paper_text_order:436", "id": "assay:1"}, {"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": ["immunotherapy efficacy were validated using immunohistochemistry assay and RNA sequencing data from IMvigor21", "ittee of Shanghai Outdo Biotech Company. 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