Low expression of leptin and its association with breast cancer: A transcriptomic study

Karim,Sajjad; Merdad,Adnan; Schulten,Hans-Juergen; Jayapal,Manikandan; Dallol,Ashraf; Buhmeida,Abdelbaset; Al-Thubaity,Fatima; Mirza,Zeenat; Gari,Mamdooh A.; Chaudhary,Adeel G.; Abuzenadah,Adel M.; Al-Qahtani,Mohammed H.

doi:10.3892/or.2016.4806

Low expression of leptin and its association with breast cancer: A transcriptomic study

Authors:
- Sajjad Karim
- Adnan Merdad
- Hans-Juergen Schulten
- Manikandan Jayapal
- Ashraf Dallol
- Abdelbaset Buhmeida
- Fatima Al-Thubaity
- Zeenat Mirza
- Mamdooh A. Gari
- Adeel G. Chaudhary
- Adel M. Abuzenadah
- Mohammed H. Al-Qahtani
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Affiliations: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
Published online on: May 13, 2016 https://doi.org/10.3892/or.2016.4806
Pages: 43-48
Copyright: © Karim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The incidence of breast cancer is alarmingly increasing worldwide and also among Saudi women. Obesity is linked with an increased cancer risk and studies have also revealed that leptin may be involved in breast tumorigenesis particularly among obese women. Numerous transcriptomic studies have been carried out worldwide; however, molecular studies among breast cancer patients of diverse ethnic groups from the Arabian Peninsula are scarce. In the present study, whole transcriptome analysis of 45 surgically resected breast tumors from Saudi Arabian female patients was carried out. Expression data were analyzed, and molecular networks and canonical pathways were identified. We identified 1,159 differentially expressed genes using p-value with a false discovery rate <0.05 and a fold-change >2 as a cut-off. Using ingenuity pathway analysis tool, we identified many canonical pathways that were implicated in breast cancer for the first time. Notably, along with other lipid metabolism molecules, leptin (LEP)was one of the most downregulated genes (fold cut-off, -7.03) with significant differences between the breast cancer and the control groups (p<0.0001) and was further confirmed in all the samples using qPCR. Transcriptomic profiling of breast cancer from a Saudi female population revealed downregulation of LEP. Molecular pathway analysis demonstrated the role of LEP and other associated molecules of the lipid metabolism pathway. Involvement of leptin and lipid metabolism in breast cancer was highlighted. The majority of cases presented were of late stage, stressing the need to educate individuals concerning early diagnostic testing and the life-style risk factors for breast cancer such as unhealthy diet and obesity.

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