Deciphering Aflatoxin B1 affected critical molecular pathways governing cancer: A bioinformatics study using CTD and PANTHER databases.

Abstract

Aflatoxin B1 (AFB1) is a fungal toxin consistently found as a contaminant in food products such as cereals, nuts, spices, and oilseeds. AFB1 exposure can lead to hepatotoxicity, cancer, immune suppression, reproductive deficiency, nutritional dysfunction, and growth impairment. AFB1 has also been listed as one of the most potent human carcinogens by the International Agency for Research on Cancer. Although the correlation between AFB1 exposure and cancer initiation and progression is already reported in the literature, very little information is available about what molecular pathways are affected during cancer development. Considering this, we first selected AFB1-responsive genes involved in five deadliest cancer types including lung, colorectal, liver, stomach, and breast cancers from the Comparative Toxicogenomics Database (CTD). Then, using the PANTHER database, a statistical overrepresentation test was performed to identify the significantly affected pathways in each cancer type. The gonadotropin-releasing hormone receptor (GnRHR) pathway, the CCKR signaling pathway, and angiogenesis were found to be the most affected pathways in lung, breast, liver, and stomach cancers. In addition, AFB1 toxicity majorly impacted apoptosis and Wnt signaling pathways in liver and stomach cancers, respectively. Moreover, the most affected pathways in colorectal cancer were the Wnt, CCKR, and GnRHR pathways. Furthermore, gene analysis was also performed for the most affected pathways associated with each cancer and identified thirteen key genes (e.g., FOS, AKT1) that may serve as biological markers for a particular type of AFB1-induced cancer as well as for in vitro AFB1 toxicological studies using specific cancer cell lines.