Delineating Potential Transcriptomic Association with Organochlorine Pesticides in the Etiology of Epithelial Ovarian Cancer
Harendra K. Shah1, Muzaffer A. Bhat3, Tusha Sharma1, Basu D. Banerjee1, *, Kiran Guleria2
1 Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences & G.T.B. Hospital (University of Delhi), Dilshad Garden, Delhi 110095, India
2 Department of Obstetrics and Gynecology, University College of Medical Sciences & G.T.B. Hospital (University of Delhi), Dilshad Garden, Delhi 110095, India.
3Department of Physiology, All India Institute of Medical Sciences, New Delhi 110029, India
Recent studies have shown that there is an increased risk of Epithelial Ovarian Cancer (EOC) with Organochlorine Pesticides (OCPs). However, the alteration in the gene expression profile has not been explored so far. The goal of the present study is to understand the probable molecular mechanism of OCPs toxicity towards discovery of dysregulation of signaling pathway associated with differential gene expression and candidate transcriptomic set of markers in the pathophysiology of EOC in OCPs exposed population.
The OCP levels were estimated by gas chromatography and whole genome differential expression study was carried out using expression microarray and candidate genes were validated using Real time RT-PCR.
Significant level of OCP residues such as β-hexachlorocyclohexane (β-HCH), Heptachlor, Heptachlor epoxide B (HTEB), dichlorodiphenyldichloroethylene (p’p’-DDE) and endosulfan-I was found between healthy and EOC patients. The transcriptome profile of several genes revealed regulation of various important cellular processes such as metabolism, inflammation, cytoskeleton dysregulation of TGF and WNT pathway in EOC cases with high OCPs.
This study provides the first evidence showing that differentially expressed genes and dysregulation of signaling pathways might be associated with significant level of OCPs exposure in ovary tissue of epithelial ovarian cancer patients. Moreover, significant correlation of these genes with OCPs revealed that OCPs exposure played vital role in dysregulation of related pathways in the etiology of EOC
Keywords: Epithelial ovarian cancer (EOC), Gene expression, Gas chromatography (GC), Microarray, Organochlorine pesticides (OCPs), Heptachlor epoxide B (HTEB).
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* Address correspondence to this author at the Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences & G.T.B. Hospital (University of Delhi), Dilshad Garden, Delhi 110095, India; Tel: +91-11-22135362; Fax: +91-11-22590495; E-mail: email@example.com