"MTHFR act as a potential cancer biomarker in immune checkpoints blockades, heterogeneity, tumor microenvironment and immune infiltration"

作者全名："Peng, Jianheng; Wu, Zhongjun"

作者地址："[Peng, Jianheng] Chongqing Med Univ, Hlth Management Ctr, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Wu, Zhongjun] Chongqing Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Chongqing 400016, Peoples R China"

通信作者："Wu, ZJ (通讯作者)，Chongqing Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Chongqing 400016, Peoples R China."

来源：DISCOVER ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001016867300001

JCR分区：Q2

影响因子：2.8

年份：2023

卷号：14

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：MTHFR; Cancer; Heterogeneity; Tumor microenvironment; Immune checkpoint blockades; Immune infiltration

摘要："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."

基金机构：Health Management discipline Promotion and Cultivation Project of Chongqing Medical University [2-01-02-03XKTS152]

基金资助正文："This work was funded by Health Management discipline Promotion and Cultivation Project of Chongqing Medical University (2-01-02-03XKTS152). The funder played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript."