Carcinogenic effects of oil dispersants: A KEGG pathway-based RNA-seq study of human airway epithelial cells

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• 作者：Yao-Zhong Liu^a ; ^{yliu8@tulane.edu} ; Lei Zhang^b ; ¹ ; Astrid M Roy-Engel^c ; Shigeki Saito^d ; Joseph A Lasky^d ; Guangdi Wang^e ; He Wang^f
• 关键词：GAGE ; generally applicable gene set enrichment ; GSNCA ; Gene Sets Net Correlations Analysis ; WAF ; water accommodated fraction ; DAVID ; database for annotation ; visualization ; and integrated discovery
• 刊名：Gene
• 出版年：2017
• 出版时间：20 February 2017
• 年：2017
• 卷：602
• 期：Complete
• 页码：16-23
• 全文大小：770 K
• 卷排序：602

文摘

The health impacts of the BP oil spill are yet to be further revealed as the toxicological effects of oil products and dispersants on human respiratory system may be latent and complex, and hence difficult to study and follow up. Here we performed RNA-seq analyses of a system of human airway epithelial cells treated with the BP crude oil and/or dispersants Corexit 9500 and Corexit 9527 that were used to help break up the oil spill. Based on the RNA-seq data, we then systemically analyzed the transcriptomic perturbations of the cells at the KEGG pathway level using two pathway-based analysis tools, GAGE (generally applicable gene set enrichment) and GSNCA (Gene Sets Net Correlations Analysis). Our results suggested a pattern of change towards carcinogenesis for the treated cells marked by upregulation of ribosomal biosynthesis (hsa03008) (p = 1.97E − 13), protein processing (hsa04141) (p = 4.09E − 7), Wnt signaling (hsa04310) (p = 6.76E − 3), neurotrophin signaling (hsa04722) (p = 7.73E − 3) and insulin signaling (hsa04910) (p = 1.16E − 2) pathways under the dispersant Corexit 9527 treatment, as identified by GAGE analysis. Furthermore, through GSNCA analysis, we identified gene co-expression changes for several KEGG cancer pathways, including small cell lung cancer pathway (hsa05222, p = 9.99E − 5), under various treatments of oil/dispersant, especially the mixture of oil and Corexit 9527. Overall, our results suggested carcinogenic effects of dispersants (in particular Corexit 9527) and their mixtures with the BP crude oil, and provided further support for more stringent safety precautions and regulations for operations involving long-term respiratory exposure to oil and dispersants.