ArticleDiscover oncology2023
MTHFR act as a potential cancer biomarker in immune checkpoints blockades, heterogeneity, tumor microenvironment and immune infiltration.
Article in Discover oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed, 5 citations in OpenAlex.
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- Climate Stressors and Physiological Dysregulations: Mechanistic Connections to Pathologies.International journal of environmental research and public health · 2023Review
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo evaluate the role and landscape of 5-10-Methylenetetrahydrofolate reductase (MTHFR) to immune infiltration, tumor microenvironment, heterogeneity, immune checkpoints blockades, prognostic significance across cancer types.
methodsData sets of genomic, transcriptomic and clinic features of MTHFR across > 60,000 patients and up to 44 cancer types were comprehensively analyzed using R software.
resultsExpression of MTHFR gene is significantly lower in 17 tumors and correlated with overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI) in specific tumors. Gene alterations of MTHFR are observed significant differences across tumor types. Expression of MTHFR is negatively correlated with the stemness index (mDNAsi, mRNAsi, DMPsi, ENHsi, EREG-mDNAsi and EREG-mRNAsi) in the most cancers. MTHFR showed significantly correlated with 67 types of immune cell infiltration scores in 44 cancer types by XCELL algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis are conducted to show the core tumor mechanism and biological process. Correlations between MTHFR and biomarkers of heterogeneity (MSI, TMB, MATH, HRD, LOH, Neoantigen, ploidy and purity) are also significant in specific tumors. MTHFR is significantly positively correlated with biomarkers of immune related genes (CD19, CD274, CD80, CD86) and mismatched repair genes (MLH1, PMS2, MSH2, MSH6, EPCAM, MLH3, PMS1, EXO1) in most cancer types. Receiver Operating Characteristics (ROC) analyses show MTHFR could act as a potential biomarker in anti-PD-1 (nivolumab to melanoma) and anti-CTLA4 (ipilimumab to melanoma) group of ontreatment, in anti-PD-1 (pembrolizumab to melanoma) group of pretreatment. Two immunohistochemistry antibodies HPA076180 and HPA077255 are verified in 20 types of tumor and could be used to detect the expression of MTHFR efficiently in clinic.
conclusionsMTHFR could predict the response of immune checkpoints blockades, heterogeneity, tumor microenvironment and immune infiltration.
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