Machine Learning and Bioinformatics Models to Identify Pathways that Mediate Influences of Welding Fumes on Cancer Progression

Abstract

AbstractWelding generates and releases fumes that are hazardous to human health. Welding fumes (WFs) are a complex mix of metallic oxides, fluorides and silicates that can cause or exacerbate health problems in exposed individuals. In particular, WF inhalation over an extended period carries an increased risk of cancer, but how WFs may influence cancer behaviour or growth is unclear. To address this issue we employed a quantitative analytical framework to identify the gene expression effects of WFs that may affect the subsequent behaviour of the cancers. We examined datasets of transcript analyses made using microarray studies of WF-exposed tissues and of cancers, including datasets from colorectal cancer (CC), prostate cancer (PC), lung cancer (LC) and gastric cancer (GC). We constructed gene-disease association networks, identified signaling and ontological pathways, clustered protein-protein interaction network using multilayer network topology, and analyzed survival function of the significant genes using Cox proportional hazards (Cox PH) model and product-limit (PL) estimator. We observed that WF exposure causes altered expression of many genes (36, 13, 25 and 17 respectively) whose expression are also altered in CC, PC, LC and GC. Gene-disease association networks, signaling and ontological pathways, protein-protein interaction network, and survival functions of the significant genes suggest ways that WFs may influence the progression of CC, PC, LC and GC. This quantitative analytical framework has identified potentially novel mechanisms by which tissue WF exposure may lead to gene expression changes in tissue gene expression that affect cancer behaviour and, thus, cancer progression, growth or establishment.