Prognostic biomarker prediction for glioma induced by heavy metals and their mixtures: An in-silico study

Abstract

Although there is an association between heavy metals and glioma, the molecular mechanisms involved in glioma development remain unclear. Therefore, this study aimed to assess the molecular mechanisms implicated in glioma development induced by heavy metals and their mixtures using various methodologies and databases (CTD, Google Scholar, PubMed, ScienceDirect, SpringerLink, miRNAsong, GeneMANIA, Metascape, MIENTURNET, UALCAN). I found that heavy metals, particularly arsenic, mercury, lead, and cadmium, as well as their mixtures, have substantial influences on the etiology of gliomas. “glioblastoma signaling pathways,” “integrated cancer pathway,” “central carbon metabolism in cancer,” “microRNAs in cancer,” “p53 signaling pathway,” “chemical carcinogenesis-DNA adducts,” “glioma,” “TP53 network,” and “MAPK signaling pathway” were the predominant molecular pathways implicated in the glioma development induced by the studied heavy metals and their mixtures. Five genes (SOD1, CAT, GSTP1, PTGS2, TNF), two miRNAs (hsa-miR-26b-5p and hsa-miR-143-3p), and transcription factors (DR1 and HNF4) were identified as key components related to combined heavy metal and glioma development. Physical interactions were found to be the most common among the heavy metals and their mixtures studied (ranging from 45.2% to 77.6%). The expression level of SOD1 was significantly lower in glioblastoma multiforma samples compared to normal samples, whereas GSTP1 and TP53 expression levels were significantly higher. Brain lower and grade glioma patients who had higher levels of TP53, hsa-miR-25, hsa-miR-34, hsa-miR-222, and hsa-miR-143 had a reduced likelihood of survival. Our findings suggest that further priority should be given to investigating the impact of specific heavy metals or their mixtures on these molecular processes.