Abstract

Hepatocellular carcinoma (HCC) is the second deadliest cancer globally, and with an estimated 782,000 new cases in 2012, it is the fifth most common cancer in men and ninth in women. HCC is of particular concern in Egypt because of the high prevalence of Hepatitis C Virus (HCV). Due to its poor prognosis, HCC is the leading cause of cancer-related deaths in Egypt. A gender disparity is observed in liver cancer cases, with higher prevalence in men by three to five fold. This sex bias is even more pronounced in mouse models of HCC, which was found to be sex hormone-dependent. Some studies have attempted to elucidate the molecular mechanisms of this disparity; but with inconclusive and sometimes contradicting outcomes, they remain largely unresolved. Understanding the natural protective mechanisms in females would allow for the development of preventative and therapeutic strategies for patients at risk for HCC or already inflicted with the disease. In this study, we applied a meta-analysis approach on already available microarray data from human normal liver tissues to identify differentially expressed genes between males and females. Microarray datasets were downloaded from the Gene Expression Omnibus database, Robust Multiarray Average pre-processed and analyzed for differential expression. The combination of 2 distinct datasets and analysis using a p-value cut-off of 0.05 and fold change cut-off of 2 revealed male up-regulated genes including RPS4Y1, EIF1AY, CYorf15B, UTY, DDX3Y and USP9Y. Female up-regulated genes included XIST, PNPLA4 and PZP. Our results confirm gender-specific differential expression patterns found in other tissues and call for further investigation using a larger sample size and more sensitive approaches such as RNA-Sequencing and, targeted protein-level studies.

Department

Biotechnology Program

Degree Name

PhD in Applied Science

Graduation Date

6-2015

Submission Date

5-28-2015

First Advisor

Rania Siam

Committee Member 1

Asma Amleh

Committee Member 2

Ramy Aziz

Extent

55 p.

Document Type

Doctoral Dissertation

Rights

The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy.

Institutional Review Board (IRB) Approval

Not necessary for this item

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