Identification of MTHFD1L as a potential biomarker for multiple cancers by pan-cancer analysis

Abstract MTHFD1L is a monofunctional enzyme, which plays a vital role in the generation of tetrahydrofolate and maintains the balance of folate cycle. In the past ten years, it was reported that MTHFD1L may participate the growth and development of cancers. HPA (Human Protein Atlas) database was used to explored the consensus MTHFD1L tissues expression and MTHFD1L gene conservation analysis. The expression of MTHFD1L in different cancer types and the relationship between the level of expression of MTHFD1L and the cancer-associated fibroblast immune infiltration were showed in the TIMER2 database. Kaplan–Meier (K-M) analysis was performed to explore prognostic value of MTHFD1L in different cancers. The cBioPortal was used to investigate the MTHFD1L genetic mutation in various tumor types of TCGA. Finally, MTHFD1L-related genes enrichment analysis was performed to study the functional mechanism of MTHFD1L in carcinogenesis. In most cancers, the mRNA expression of MTHFD1L is higher in the tumor tissues compared to the normal tissues. Besides, higher expressions of MTHFD1L were significantly associated with shorter OS in ACC, BLCA, BRCA, CESC, HNSC, LGG, LIHC, LUAD, SKCM and shorter DFS in ACC, BLCA, CESC, LGG, PRAD and SKCM. The high expression of MTHDF1L was related to the advanced stage of BLCA, LIHC, LUAD, OV, SKCM, UCEC and UCS significantly. What’s more, MTHDF1L expression was positively linked with cancer-associated fibroblast infiltration in HNSC, KIRC, KIRP, LUAD and PAAD. The GO biological process (BP) enrichment includes mitotic cell cycle, cell cycle, mitotic cell cycle process and so on. MTHDF1L physically interacts with CLPP, CS, LRPPRC and MTIF2. This pan-cancer investigation suggested the prognostic value and oncogenic role of MTHFD1L for multiple tumor types.