MDIG, a 2‑oxoglutarate‑dependent oxygenase, acts as an oncogene and predicts the prognosis of multiple types of cancer.

Abstract

Recent studies have indicated that mineral dust-induced gene (MDIG) is an oncogene induced by environmental factors, which has a key role in the development and progression of various tumor types, through epigenetic modifications; however, there are no previous pan-cancer analyses of MDIG. In the present study, a comprehensive pan-cancer analysis of MDIG was performed using public databases. The results demonstrated that MDIG was upregulated in tumor tissue samples compared with normal tissue, that it was present in all cancer cell lines and it was closely associated with the prognosis of patients with different tumor types. Furthermore, MDIG expression was closely associated with the immunological characteristics of the tumor microenvironment (TME), such as the frequency of tumor-infiltrating immune cells, TME-relevant signatures, immunostimulatory genes, immune checkpoint genes, chemokine receptor genes, tumor mutational burden and microsatellite instability. In parallel, high expression of MDIG was associated with improved overall survival of patients and this was verified in a cohort of patients who had received anti-programmed cell death 1 ligand 1 treatment. Furthermore, high expression of MDIG led to multiple drug resistance in The Cancer Genome Atlas-lung adenocarcinoma cohort. In addition, gene set variant analysis and gene set enrichment analysis indicated that MDIG was involved in cell cycle regulation. In vitro experiments suggested that MDIG promoted cell proliferation through the mTOR complex 2/Akt and pyruvate dehydrogenase kinase 1/Akt signaling pathways. In summary, the present study suggests that MDIG may be a prognostic biomarker and therapeutic target for various cancer types.