title: Low expression of leptin and its association with breast cancer: A transcriptomic study.
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.
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Sajjad
authors.initials: S
authors.lastname: Karim
authors.affiliation: Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Adnan
authors.initials: A
authors.lastname: Merdad
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Schulten
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Manikandan
authors.initials: M
authors.lastname: Jayapal
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Dallol
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Abdelbaset
authors.initials: A
authors.lastname: Buhmeida
authors.affiliation: Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Fatima
authors.initials: F
authors.lastname: Al-Thubaity
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Mirza
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Mamdooh A
authors.initials: MA
authors.lastname: Gari
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Adeel G
authors.initials: AG
authors.lastname: Chaudhary
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Adel M
authors.initials: AM
authors.lastname: Abuzenadah
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Al-Qahtani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D020738:Leptin / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics*; D008875:Middle Aged; D054411:Receptors, Leptin / Q000235:genetics*; D012529:Saudi Arabia; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D020738:Leptin; D054411:Receptors, Leptin