Adnan Merdad

Transcriptomics profiling study of breast cancer from Kingdom of Saudi Arabia revealed altered expression of Adiponectin and Fatty Acid Binding Protein4 : Is lipid metabolism associated with breast cancer?

BackgroundBreast cancer incidence rates are increasing at an alarming rate among Saudi Arabian females. Most molecular genetic discoveries on breast cancer and other cancers have arisen from studies examining European and American patients. However, possibility of specific changes in molecular signature among cancer patients of diverse ethnic groups remains largely unexplored. We performed transcriptomic profiling of surgically-resected breast tumors from 45 patients based in the Western region of Saudi Arabia using Affymetrix Gene 1.0 ST chip. Pathway and biological function-based clustering was apparent across the tissue samples.ResultsPathway analysis revealed canonical pathways that had not been previously implicated in breast cancer. Biological network analysis of differentially regulated genes revealed that Fatty acid binding protein 4, adipocyte (FABP4), adiponectin (ADIPOQ), and retinol binding protein 4 (RBP4) were most down regulated genes, sharing strong connection with the other molecules of lipid metabolism pathway. The marked biological difference in the signatures uncovered between the USA and Saudi samples underpins the importance of this study. Connectivity Map identified compounds that could reverse an observed gene expression signatureConclusionsThis study describes, to our knowledge, the first genome-wide profiling of breast cancer from Saudi ethnic females. We demonstrate the involvement of the lipid metabolism pathway in the pathogenesis of breast cancer from this region. This finding also highlights the need for strategies to curb the increasing rates of incidence of this disease by educating the public about life-style risk factors such as unhealthy diet and obesity.

Characterization of familial breast cancer in Saudi Arabia

BackgroundThe contribution of genetic factors to the development of breast cancer in the admixed and consanguineous population of the western region of Saudi Arabia is thought to be significant as the disease is early onset. The current protocols of continuous clinical follow-up of relatives of such patients are costly and cause a burden on the usually over-stretched medical resources. Discovering the significant contribution of BRCA1/2 mutations to breast cancer susceptibility allowed for the design of genetic tests that allows the medical practitioner to focus the care for those who need it most. However, BRCA1/2 mutations do not account for all breast cancer susceptibility genes and there are other genetic factors, known and unknown that may play a role in the development of such disease. The advent of whole-exome sequencing is offering a unique opportunity to identify the breast cancer susceptibility genes in each family of sufferers. The polymorphisms/mutations identified will then allow for personalizing the genetic screening tests accordingly. To this end, we have performed whole-exome sequencing of seven breast cancer patients with positive family history of the disease using the Agilent SureSelect™ Whole-Exome Enrichment kit and sequencing on the SOLiD™ platform.ResultsWe have identified several coding single nucleotide variations that were either novel or rare affecting genes controlling DNA repair in the BRCA1/2 pathway.ConclusionThe disruption of DNA repair pathways is very likely to contribute to breast cancer susceptibility in the Saudi population.

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

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.

The desire to utilize postmastectomy breast reconstruction in Saudi Arabian women. Predictors and barriers

Objectives: To study factors that influence the desire to utilize breast reconstruction after mastectomy, and to investigate the barriers to reconstruction among women in Saudi Arabia. Methods: We conducted a cross-sectional study at 2 surgical centers in Jeddah, Saudi Arabia. A self-administered questionnaire was distributed to all breast cancer patients attending the surgery clinics for follow-up after mastectomy between January and March 2013. Ninety-one patients met the study inclusion criteria. The first part of the questionnaire covered the demographic and socioeconomic information regarding factors that might influence the desire to utilize breast reconstruction including possible barriers. Multivariate logistic regression was used to determine the significant predictors of the desire to undergo reconstruction. Results: Overall, 16.5% of patients underwent breast reconstruction after mastectomy. Young age and high educational attainment were significantly associated with an increased desire to undergo reconstruction. The main barriers to reconstruction were the lack of adequate information on the procedure (63%), concerns on the complications of the procedure (68%), and concerns on the reconstruction interfering with the detection of recurrence (54%). Conclusion: Age and educational level were significant predictors of the desire to utilize breast reconstruction. Furthermore, modifiable barriers included the lack of knowledge and misconceptions on the procedure. Addressing these issues may increase the rate of breast reconstruction in Saudi Arabia.

Detection of rare single nucleotide variants affecting genes in the DNA repair pathways in hereditary breast cancer

Background Patients with hereditary breast cancer constitute a considerable fraction of overall breast cancer sufferers. The contribution of genetic factors to the development of breast cancer in the admixed and highly consanguineous population of the western region of Saudi Arabia is thought to be significant as the disease is early onset [1]. The current protocols of continuous clinical follow-up of relatives of such patients are costly and cause a burden on the usually over-stretched medical resources. Discovering the significant contribution of BRCA1/2 mutations to breast cancer susceptibility allowed for the design of genetic tests that allows the medical practitioner to focus the care for those who need it most. However, BRCA1/2 mutations do not account for all breast cancer susceptibility genes and there are other genetic factors, known and unknown that may play a role in the development of such disease.

Identification of frequent MTNR1B methylation in breast cancer following the application of high-throughput methylome analysis

Background Breast cancer is the main cancer type affecting women in the Kingdom of Saudi Arabia. The relatively young age of onset in this population could be explained by the interplay between common genetic susceptibility background substantiated by increased consanguinity and epigenetic aberrations caused by the shift in life style experienced in this region [1]. Genomic screening of breast cancer patients is beneficial in identifying underlying variants that could explain increased susceptibility to breast cancer. However, it is important to understand the epigenetic aberrations associated with breast cancer in order to shed light on its etiology and identify possible treatments. To this end, we have performed MBD-Seq on a cohort of breast cancer samples that led to the identification of tumor-specific methylation of the MTNR1B promoter in a significant number of breast cancer cases from Saudi Arabia.

Gene expression profiling of lymph node positive-negative metastasis of primary breast cancer in Saudi Arabian patients

Background Breast cancer is the most frequent and most deadly cancer in females and incidence rates are increasing at an alarming rate in Saudi Arabia [1]. Studies have shown the potential of gene expression profiling in discovering biomarkers and molecular genetic signatures for breast cancer [2-4]. However, such discoveries and association of expression profiling with different type of Saudi Arabian breast cancer patients are largely unexplored.

Airgun injuries: A national health hazard.

Between 1983 and 1989, 41 patients were admitted to King Fahad Hospital (KFH) in Al-Baha, Saudi Arabia with airgun injuries. Of the patients admitted, 83% were under 18 years of age. The majority of injuries (80.5%) were trivial. However, 19.5% had serious injuries that required major surgery. These injuries were considered potentially lethal. Public education via media will probably be effective in reducing the number of injuries caused by these weapons.

Management of Postoperative Gastrointestinal Leakage With Autologous Stromal Vascular Fraction

To assess the efficacy of using autologous stromal vascular fraction (SVF) to promote healing of controlled fistula tracts in the management of postoperative upper gastrointestinal leakage. This is an experimental study conducted on 10 experimental rabbits. Animal models were divided into the SVF group which received an autologous SVF and the control group which did not receive the implantation. Surgery was performed on both groups to induce a gastric leak and create a controlled fistula tract between the leakage site in the stomach and the skin. After 2 weeks, surgery was performed on the SVF group to harvest, process and then implant the autologous SVF in the fistula tract. Animal models were followed up and their fistula tracts were evaluated for healing by gross and microscopic examination of the fistula tracts before the SVF implantation and at 24 hours, 1 week, 2 weeks and 3 weeks after implantation. The control group revealed no closure of fistula tracts by the 3(rd) week after implantation and there were no signs of inflammation or drainage. On the other hand, the SVF group showed signs of healing process with progressive closure of the fistula tract to about 95% by the 3(rd) week after implantation. The use of autologous SVF implantation to promote the healing of controlled fistula tracts seems to be a novel, safe and effective method in the management of postoperative upper gastrointestinal leakage. It could prevent reoperation and reduce hospital stay, morbidity and mortality. These results are promising and provide support for further clinical studies.

Prognostic significance of fibroblast growth factor 19 (FGF19) expression in breast invasive ductal carcinoma

Materials and methods Archival FFPE tumor samples were analyzed using immunohistochemistry (IHC) for monoclonal antiFGF19 (W12) antibody in 193 patients with BC. IHC analysis was done using the automatic system (BenchMark XT; Ventana Medical Systems, Inc. Tucson, AZ, USA). Patients were diagnosed and treated at the Departments of Pathology, Surgery and Oncology, King Abdulaziz University Hospital, Saudi Arabia and the National Oncology Institute, Sabratha, Libya during years 2000-2008.