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Leila Arfaoui,1 Areej Alkhaldy,1 Ahad Alareeshi,1 Ghadeer AlSaadi,1 Shaima Alhendi,1 Afnan Alghanmi,1 Wejdan Alghafari,1 Mourad Assidi2,3 1Clinical Nutrition Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 2Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 3Medical Laboratory Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi ArabiaCorrespondence: Leila Arfaoui Tel +966 126401000 (ext. 41612)Email leila.arfaoui@gmail.comBackground: Few studies have investigated the knowledge and attitudes towards the nutrition facts label, the nutrient content and health claims (NHCs) among consumers from different countries/cultures.Methods: This cross-sectional study assessed the knowledge and self-reported use of the nutrition facts label and NHCs among Saudi adults. A total of 722 participants were recruited using an online questionnaire.Results: Total knowledge score was 5.8 ± 2.5/13 points (45%). Approximately, 18%, 77%, and 5% of the participants had low, medium, and high levels of knowledge, respectively. Participants were more knowledgeable on the nutrition facts label (2.6 ± 1.6/5 points) and health claims (2.7 ± 1.2/4 points) versus nutrient content claims (0.5 ± 0.7/4 points). The total use score was 20.1 ± 5.7/30 points (67%); approximately, 2%, 61%, and 37% of the participants were classified as low, medium, and high use level, respectively. Participants’ use of the nutrition facts label, nutrient content claims, and health claims was 10.0 ± 3.1/15, 6.5 ± 2.2/9, and 3.6 ± 1.8/6 points, respectively.Conclusion: This study highlights the need for more education and public awareness programs to enhance consumer knowledge and use of the nutrition facts label and NHCs, and consequently lead to healthy dietary choices.Keywords: health claims, knowledge, nutrition facts label, nutrient claims, nutritional information

Despite the significant achievements of current healthcare systems (CHCSs) in curing or treating several acute conditions, there has been far less success coping with noncommunicable diseases (NCDs), which have complex roots and nonconventional transmission vectors. Owing to the impact of the invisible hyperendemic NCDs and the COVID-19 pandemic, the limitations of CHCSs have been exposed. In contrast, the advent of omics-based technologies and big data science has raised global hope of curing or treating NCDs and improving overall healthcare outcomes. However, challenges related to their use and effectiveness must be addressed. Additionally, while such advancements intend to improve quality of life, they can also contribute the ever-increasing health disparity among vulnerable populations, such as low/middle-income populations, poorly educated people, gender-based violence victims, and minority and indigenous peoples, to name a few. Among five health determinants, the contribution of medical care to individual health does not exceed 11%. Therefore, it is time to implement a new well-being-oriented system complementary or parallel to CHCSs that incorporates all five health determinants to tackle NCDs and unforeseen diseases of the future, as well as to promote cost-effective, accessible, and sustainable healthy lifestyle choices that can reduce the current level of healthcare inequity.

The present study investigated the associations of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels with clinicopathological variables and survival outcomes in Libyan patients with pancreatic ductal adenocarcinoma (PDAC). The clinicopathological variables of 123 patients with PDAC registered at the National Cancer Institute in Misurata, Libya, between 2010 and 2018 were retrospectively analyzed. Blood samples from these patients were analyzed for serum CEA and CA19-9 levels before treatment by electrochemiluminescence immunoassay (double antibody sandwich ELISA) on a Roche cobas e 602 modules. The relationships between CA19-9 and CEA serum levels with clinicopathologic variables and survival outcomes were analyzed using the Kaplan-Meier method, log-rank test and Cox regression analyzes. Cut-off values for serum CEA and CA19-9 levels were 5 ng/ml and 400 U/ml, respectively. The median serum levels of all patients with PDAC for CEA and CA19-9 were 8 ng/ml (1.1-377 ng/ml) and 389 U/ml (1-10,050 U/ml), respectively. Tumors with higher serum CEA and CA19-9 levels were found in 63 and 48% of patients, respectively. Higher CEA and CA19-9 serum levels were significantly associated with more indicators of a malignant phenotype, including a surgically unresectable tumor, unevaluable lymph nodes, advanced stages and distant metastases. Regarding survival, patients with higher serum levels of the biomarkers CEA and CA19-9 had shorter overall survival rates (P0.016 and (P0.014, log-rank, respectively) and lower disease-free survival rates (P0.002 and P0.0001, log-rank, respectively)

Breast cancer (BC) in women is the second most commonly diagnosed type of cancer worldwide, and the leading cause of cancer-related mortality among women. To date, surgery is the main treatment option, often combined with other (neo)adjuvant therapeutic modalities to treat this malignancy and prevent relapse. Despite the invasive aspects of the majority of these therapeutic interventions and their associated side-effects, these treatments are still unable to effectively cure this disease and prevent relapse. Thus, there is an urgent need for the identification of more relevant biomarkers for more effective theranostics. Signaling lymphocytic activation molecule F7 (SLAMF7) is a glycosylated cell surface protein that plays a critical role in immune cell functions under both healthy conditions and in cancer. It is specifically targeted by elotuzumab for the treatment of multiple myeloma. The present retrospective study aimed to investigate the expression patterns of SLAMF7 and evaluate its associations with clinicopathological features, including the survival outcomes of patients with BC. The protein expression of SLAMF7 in BC was investigated in 278 lymph node-positive formalin-fixed and paraffin-embedded (FFPE) tissue blocks using tissue microarray and immunohistochemistry techniques. The results revealed a significant association between cytoplasmic SLAMF7 protein expression and several clinicopathological parameters, particularly age at diagnosis (P0.007), tumor invasion (P0.008) and vascular invasion (P=0.05). Kaplan-Meier analysis revealed that the overexpression of SLAMF7 was a strong positive prognosticator of both disease-free and disease-specific survival in the patients with BC (log-rank P=0.001 and P=0.008, respectively). This suggests that patients with SLAMF7 protein expression have a higher survival rate and a lower recurrence rate. On the whole, the present study demonstrated that a weak or no SLAMF7 expression was a powerful prognosticator of poor survival outcomes associated with both tumor and vascular invasion. Therefore, elotuzumab (as SLAMF7monoclonal antibody therapy) may be a promising option for targeted therapy worthy of clinical testing in patients with BC.

Next-Generation Sequencing allows for quick and precise sequencing of multiple genes concurrently. Recently, this technology has been employed for the identification of novel gene mutations responsible for disease manifestation among breast cancer (BC) patients, the most common type of cancer amongst Arabian women, and the major cause of disease-associated death in women worldwide. Genomic DNA was extracted from the peripheral blood of 32 Saudi Arabian BC patients with histologically confirmed invasive BC stages I-III and IV, as well from 32 healthy Saudi Arabian women using a QIAamp

The diagnostic and prognostic utility of circulating cell-free DNA (cfDNA) in breast cancer (BC) patients was recently reported. Here, we investigated the use of cfDNA to examine microsatellite instability (MSI) and loss of heterozygosity (LOH) for early BC diagnosis. cfDNA and genomic DNA from 41 female BC patients and 40 healthy controls were quantified using NanoDrop spectrophotometry and real-time PCR. The stability of genomic and cfDNA was assessed using a high-resolution AmpFlSTR MiniFiler human identification kit. Significant increases in cfDNA plasma concentrations were observed in BC patients compared to controls. The genotype distribution of the eight autosomal short tandem repeat (STR) loci D7S820, D13S317, D21S11, D2S1338, D18S51, D16S539, FGA, and CSF1PO were in Hardy–Weinberg equilibrium. Significant differences in the allele frequencies of D7S820 allele-8, D21S11 allele-29, allele-30.2, allele-32.2, and CSF1PO allele-11 were seen between BC patients and controls. LOH and MSI were detected in 36.6% of the cfDNA of patients compared to genomic DNA. This study highlights the utility of plasma-derived cfDNA for earlier, less invasive, and cost-effective cancer diagnosis and molecular stratification. It also highlights the potential value of cfDNA in molecular profiling and biomarkers discovery in precision and forensic medicine.

Ovarian cancer (OC) is the deadliest among all gynecological cancers. Epidemiological studies showed that obesity might influence many cancers including OC. One of the key factors that may link obesity and OC is leptin (LEP), known as an adipokine with pleiotropic effects on body homeostasis. This study aims to investigate the expression pattern of LEP, assess the methylation profiles of LEP and their associations with clinicopathological features including survival outcomes of OC patients. The protein expression of LEP was evaluated in 208 samples using both tissue microarray and immunohistochemistry techniques. The methylation profiles of LEP were measured in 63 formalin-fixed, paraffin-embedded tumor tissues by quantitative polymerase chain reaction using a MethyLight assay. Our results showed a significant association of LEP protein overexpression with several clinicopathological variables, mainly tumor subtype, LVI, age of menarche, tumor size and stage (p < 0.04). Kaplan–Meier analysis (using low expression versus high expression as a discriminator) indicated that LEP protein overexpression is a powerful positive prognosticator of both OC recurrence (DFS) and disease-specific survival (DSS) in our OC cohort (log-rank p = 0.01 and p = 0.002, respectively). This implies that patients with high LEP expression profiles live longer with less recurrence rates. Methylation analysis results demonstrated a clear association between no/low LEP protein expression pattern (38%) and LEP promoter CpG island hypermethylation (43%). Results of this study suggest that LEP is a powerful prognosticator of OC recurrence and DSS. LEP expression in OC seems to be regulated by its promoter hypermethylation through gene partial/total silencing. Further multi-institutional studies using larger cohorts are required to demystify the intricate molecular functions of this leptin-driven effects in OC pathophysiology and to accurately assess its theranostic potential and validate its prognostic/predictive power in OC onset, progression towards more effective and personalized management of OC patients.

Background: TIMP3 is a multifunctional proteolytic enzyme belonging to TIMPs family and acts as a potent inhibitor of matrix metalloproteinases (MMPs). TIMP3 possesses a tumor suppresive function by directly promoting tumor cell apoptosis, preventing angiogenesis and extracellular matrix remodelling. The lower expression of TIMP3 was associated with poor prognosis and overall survival in various cancer types. The aim of this study was to evaluate the association of TIMP3 protein expression with ovarian cancer (OC) clinicopathological features and survival outcomes. Patients and Methods: One hundred forty four of OC FFPE samples were collected from King Abdulaziz University Hospital, Saudi Arabia and constructed in tissue microarray (TMA) slides. Automated Ventana immunostainer platform was used to evaluate TIMP3 protein expression patterns. Results: The study showed that TIMP3 exhibits cytoplasmic localisation. This TIMP3 protein expres- sion was not associated with age, tumor size and the involvement of lymph nodes (p > 0.05). However, it was significantly correlated with tumor stage (p < 0.05) and borderline significant with endpoint status (p = 0.07). Interestingly, the Kaplan-Meier analysis of disease specific survival (DSS) outcomes showed a significant association (p = 0.02, log rank) between OC patients with higher TIMP3 expression compared to those with lower expression. In fact, OC patients with high TIMP3 expression had longer survivals. Multivariate Cox’s regression analysis suggests that low TIMP3 protein expression pattern is an independent poor survival marker (p = 0.025). Conclusion: Cytoplasmic TIMP3 protein expression could be used as a good prognosticator to stratify poorly prognostic OC patients in order to personlaize their disease management.

The extracellular matrix (ECM) disruption and cytoskeleton reorganization are crucial events in tumor proliferation and invasion. E-Cadherin (E-CAD) is a member of cell adhesion molecules involved in cell-cell junctions and ECM stability. The loss of E-CAD expression is associated with cancer progression and metastasis. This retrospective study aimed to assess E-CAD protein expression in ovarian cancer (OC) tissues and to evaluate its prognostic value. Patients and Methods: 143 formalin-fixed and paraffin-embedded (FFPE) blocks of primary advanced stages OC were retrieved and used to construct Tissue microarrays. Automated immunohistochemistry technique was performed to evaluate E-CAD protein expression patterns in OC. Results: E-CAD protein expression was significantly correlated with OC histological subtype (p

In the present study, the Risk Malignancy Index (RMI) was calculated based on menopausal status, ultrasound (US) findings and serum biological cancer antigen 125 (CA-125) levels as a scoring system in Libyan females with ovarian masses (OMs) to differentiate between benign and malignant tumors. A total of 51 females with OMs referred to the Gynaecology Department of the National Cancer Institute in Misurata (Libya) between January 2019 and December 2020 were retrospectively reviewed for diagnostic testing. Clinicopathological and demographic data were obtained from patient records. A cut-off point of RMI=200 was used to differentiate between benign and malignant tumors. The mean age of the patients was 47 years (range, 19-90 years) and 60% of the patients were premenopausal. Examination of the four RMI indices and disease status indicated that the association with the US score (P0.0001) and with CA-125 (P=0.017) was highly significant. However, the age at diagnosis and menopausal status did not have any significant association with the disease status. The RMI with a cut-off point of 200 had a sensitivity and specificity of 87.5 and 90.7%, respectively, and a positive and negative predictive value of 63.6 and 97.5%, respectively. The association between the RMI and disease status was highly significant (P0.0001). In conclusion, the RMI appears to be a reliable, simple and cost-effective tool for clinical differentiation between benign and malignant OMs. This may help to improve the optimal diagnosis and planning of an individualized treatment strategy. However, given the small sample size of the cohort, further validation using larger cohorts in other settings is recommended.

Among all gynecological cancers, ovarian cancer (OC) is one of the deadliest types of cancer worldwide. Epigenetic silencing of some genes has been reported to be associated with OC. In this context, Klotho (KL) gene methylation is a promising biomarker for OC. The present study aimed to investigate the methylation profiles of KL and assess its prognostic value. A total of 63 formalin-fixed paraffin-embedded tissue samples from patients with primary OC were collected and analyzed in the present study. The methylation profiles of KL were assessed by performing DNA bisulfate treatment followed by DNA promoter methylation analysis using the MethyLight assay. The results revealed KL promoter hypermethylation in 62% of the OC cohort. Additionally, significant associations were observed between KL methylation profiles and tumor subtype (P

Khat (Catha edulis (Vahl) Endl.) is an evergreen flowering shrub used as a stimulant in many regions worldwide including East Africa, the Arabian Peninsula, Europe, and the United States. Chewing leaves of khat induces excitement and euphoria, which are primarily attributed to two major constituents, cathinone and cathine. Khat also contains other important constituents such as cathedulins. A considerable number of studies reported side effects induced by the khat extracts to both embryos and adults. These include teratogenicity and developmental retardation, oral cancer and ulcers, high blood pressure, and myocardial infarction. So far, little attention has been paid to the effects of khat extracts on the molecular signaling interactions. We aimed in this study to investigate this through evaluating the effects of khat extracts on SKOV3, a human ovarian adenocarcinoma cell line. We show, by in vitro assays, that khat induces several cellular defects including reduced cell size, cell membrane damage, and apoptosis. At high khat extract concentrations, the cell metabolic activity, cell cycle, and cellular proliferation were affected. RT-qPCR analysis showed an increase in the gene expression of the apoptotic marker BAX, the tumor suppressor p53, and the inflammatory cytokine IL-6. Protein expression analysis by immunostaining showed downregulation of β-catenin, E-cadherin, and Ki-67 and upregulation of FZD8 and SPRY2, suggesting that Wnt and FGF signaling were implicated. SwissTargetPrediction in silico analysis showed that khat constituents cathine, cathinone, catheduline K2, and catheduline E5 bind to family A G-protein-coupled receptor, cause many neurological diseases and disorders such as Alzheimer's, schizophrenia, depression, and anxiety, and induce many ovarian cancer-related diseases. The analysis also showed that important signaling pathways such as CREB, Wnt, FGF, IL-6, and ERK/MAPK, and that of the endometrial cancer, and cell cycle were implicated. Upstream regulators of cathine and cathinone were found to potentially target several molecules including interleukin-8, MMP2, PLAU, and micro-RNAs. In conclusion, khat induces significant cellular and molecular changes that could potentially cause a wide range of serious diseases and syndromes. Such an impact could have a heavy burden on the health care system in the countries where khat is consumed.

Gut microbiota and their metabolites play a vital role in colon health and disease. Accumulating evidence suggests that the gut microbiota contributes to the risk of colorectal cancer (CRC). However, the role of a specific microbial community together with their metabolites contributing to the risk, initiation and progression of CRC is still unknown. Hence, we used a Bayesian Networks in combination with the IDA (Intervention calculus when the DAG is absent) to generate a graphical model that allows causal relationships to be inferred from observational data. Results from the analysis of publically available datasets showed that four species: Fusobacteium, Citrobacter, Microbacterium and Slaxkia have estimated non-null lower bounds of causal effects of CRC. These findings support the hypothesis that specific bacterial species (microbial markers) act in concert with locally modified microbiota to cause or influence CRC progression. Additional comprehensive studies are required to validate the potential use of F. nucleatum, Citrobacter as well as Slackia as microbial biomarkers in CRC for prevention, diagnosis, prognosis and/or therapeutics.

Background Preterm birth (PTB), birth at

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Traditionally, the success of a researcher is assessed by the number of publications he or she publishes in peer-reviewed, indexed, high impact journals. This essential yardstick, often referred to as the impact of a specific researcher, is assessed through the use of various metrics. While researchers may be acquainted with such matrices, many do not know how to use them to enhance their careers. In addition to these metrics, a number of other factors should be taken into consideration to objectively evaluate a scientist′s profile as a researcher and academician. Moreover, each metric has its own limitations that need to be considered when selecting an appropriate metric for evaluation. This paper provides a broad overview of the wide array of metrics currently in use in academia and research. Popular metrics are discussed and defined, including traditional metrics and article-level metrics, some of which are applied to researchers for a greater understanding of a particular concept, including varicocele that is the thematic area of this Special Issue of Asian Journal of Andrology. We recommend the combined use of quantitative and qualitative evaluation using judiciously selected metrics for a more objective assessment of scholarly output and research impact

Human epidermal growth factor recptor-2 (HER2) was identified as a driver gene in several types of cancers with both prognostic and predictive value. However, the molecular association of HER2 gene mutation with HER2 gene amplification and/or protein expression in cancer tissues has not been clearly defined. Moreover, there is little information available on HER2 status role in tumor progression and metastasis in colorectal carcinoma (CRC) compared to other solid tumors. The aim of this study was to evaluate both HER2 amplification and protein expression profiles using immunohistochemistry (IHC) and bright-field dual in situ hybridization (BDISH) techniques, respectively.Tissue microarray (TMA) was constructed to accommodate a total of 243 CRC formalin-fixed paraffin embedded (FFPE) samples of consent patients and stained by IHC and BDISH methods. The expression patterns of HER2 protein status were evaluated and correlated to HER2 gene amplification status and then assessed for its prognostic value.The expression profile of 58% samples showed cytoplasmic expression patterns of different categories. Interestingly, only 1% showed strong (+3) membranous expression pattern of HER2 with perfect match with their corresponding gene amplification status (2). However, the cytoplasmic HER2 protein status did not show significant correlation with most clinicopathological features and survival outcomes except with age (p = 0.04) and tumor size (p = 0.03).We demonstrated that the membranous HER2 gene/protein status is infrequent, while the main fraction of HER2 overexpression was cytoplasmic and lacking prognostic value. This cytoplasmic HER2 overexpression was induced through a gene-amplification independent pathway, making the HER2 gene status evaluation approach in those cases not worthy. Further investigations about the molecular pathways of the cytoplasmic HER2 protein in CRC and its associations with survival outcomes are required to allow either a breakthrough in CRC management; or to confirm the hypothesis of a marginal role in CRC onset and progression.

Invasive ductal carcinoma of the breast is the most common cancer affecting women worldwide. The marked heterogeneity of breast cancer is matched only with the heterogeneity in its associated or causative factors. Breast cancer in Saudi Arabia is apparently an early onset with many of the affected females diagnosed before they reach the age of 50 years. One possible rationale underlying this observation is that consanguinity, which is widely spread in the Saudi community, is causing the accumulation of yet undetermined cancer susceptibility mutations. Another factor could be the accumulation of epigenetic aberrations caused by the shift toward a Western-like lifestyle in the past two decades. In order to shed some light into the molecular mechanisms underlying breast cancer in the Saudi community, we identified KLOTHO (KL) as a tumor-specific methylated gene using genome-wide methylation analysis of primary breast tumors utilizing the MBD-seq approach. KL methylation was frequent as it was detected in 55.3 % of breast cancer cases from Saudi Arabia (n = 179) using MethyLight assay. Furthermore, KL is downregulated in breast tumors with its expression induced following treatment with 5-azacytidine. The involvement of KL in breast cancer led us to investigate its relationship in the context of breast cancer, with one of the protagonists of its function, fibroblast growth factor receptor 4 (FGFR4). Overexpression of FGFR4 in breast cancer is frequent in our cohort and this overexpression is associated with poor overall survival. Interestingly, FGFR4 expression is higher in the absence of KL methylation and lower when KL is methylated and presumably silenced, which is suggestive of an intricate relationship between the two factors. In conclusion, our findings further implicate "metabolic" genes or pathways in breast cancer that are disrupted by epigenetic mechanisms and could provide new avenues for understanding this disease in a new context.

DiGeorge syndrome (DGS) is a genetic disorder known as a clinically variable syndrome with over 180 associated phenotypic features. It is caused by a common human deletion in the 22q11.2 chromosomal region and currently is affecting approximately 1 in 4,000 individuals. Despite the prevalence of inherited diseases mainly due to consanguineous marriages, the current diagnosis of DGS in Saudi Arabia is mainly based on conventional high-resolution chromosome banding (karyotyping) and FISH techniques. However, advanced genome-wide studies for detecting microdeletions or duplications across the whole genome are needed. The aim of this study is to implement and use aCGH technology in clinical diagnosis of the 22q11.2 deletion in Saudi Arabian DGS patients and to confirm its effectiveness compared to conventional FISH and chromosome banding techniques. Thirty suspected DGS patients were assessed for chromosome 22q11.2 deletion using high-resolution G-banding, FISH, and aCGH. The aCGH results were compared with those obtained by the other 2 cytogenetic techniques. G-banding detected the 22q11.2 deletion in only 1 patient in the cohort. Moreover, it detected additional chromosomal aberrations in 3 other patients. Using FISH, allowed for detection of the 22q11.2 deletion in 2 out of 30 patients. Interestingly, the use of aCGH technique showed deletions in the chromosome 22q11.2 region in 8 patients, indicating a 4-fold increase in diagnostic detection capacity compared to FISH. Our results show the effectiveness of aCGH to overcome the limitations of FISH and G-banding in terms of diagnostic yield and allow whole genome screening and detection of a larger number of deletions and/or duplications in Saudi Arabian DGS patients. Except for balanced translocations and inversions, our data demonstrate the suitability of aCGH in the diagnostics of submicroscopic deletion syndromes such as DGS and most chromosomal aberrations or complex abnormalities scattered throughout the human genome. Our results recommend the implementation of aCGH in clinical genomic testing in Saudi Arabia to improve the diagnostic capabilities of health services while maintaining the use of conventional cytogenetic techniques for subsequent validation or for specific and known aberrations whenever required.

Particulate matter (PM) contains heavy metals that affect various cellular functions and gene expression associated with an array of acute and chronic diseases, in humans. However, their specific effects on the stem cells remain unclear. Here, we report the effects of PM collected from Jeddah city on bone marrow mesenchymal stem cells (BM-MSCs) on proliferation, cell death, related gene expression and systems biological analysis aiming to understand the underlying mechanisms. Two different sizes (PM2.5-10) were tested in vitro at various concentrations (15 to 300 µg/ml) and durations (24 to 72 h). PMs induced cellular stress including membrane damage, shrinkage and death. Lower concentrations of PM2.5 increased BM-MSCs proliferation, while higher concentrations decreased it. PM10 decreased BM-MSCs proliferation in a concentration-dependant manner. The X-Ray Fluorescence spectrometric analysis showed that PM contains high levels of heavy metals. Ingenuity Pathway Analysis (IPA) and hierarchical clustering analyses showed that heavy metals were associated with signalling pathways involving cell stress/death, cancer and chronic diseases. qRT-PCR results showed differential regulation of the apoptosis genes (BCL2, BAX); upregulation of inflammation associated genes (TNF-a and IL-6) and downregulation of cell cycle regulation gene (P53). We conclude that PM could affect different cellular functions and predispose to debilitating diseases.

Stratification of colorectal cancer for better management and tangible clinical outcomes is lacking in clinical practice. To reach this goal, the identification of reliable biomarker(s) is a prerequisite to deliver personalized colorectal cancer theranostics. Osteopontin (SPP1) is a key extracellular matrix protein involved in several pathophysiological processes including cancer progression and metastasis. However, the exact molecular mechanisms regulating its expression, localization, and molecular functions in cancer are still poorly understood. This study was designed to investigate the SPP1 expression profiles in Saudi colorectal cancer patients, and to assess its prognostic value. Hundred thirty-four (134) archival paraffin blocks of colorectal cancer were collected from King Abdulaziz University Hospital, Saudi Arabia. Tissue microarrays were constructed, and automated immunohistochemistry was performed to evaluate SPP1 protein expression patterns in colorectal cancer. About 20% and 23% of our colorectal cancer samples showed high SPP1 cytoplasmic and nuclear expression patterns, respectively. Cytoplasmic SPP1 did not correlate with age, gender, tumor size, and location. However, significant correlations were observed with tumor grade ( p = 0.008), tumor invasion ( p = 0.01), and distant metastasis ( p = 0.04). Kaplan–Meier survival analysis showed a significantly lower recurrence rate in patients with higher SPP1 cytoplasmic expression ( p = 0.05). At multivariate analysis, high SPP1 cytoplasmic expression was an independent favorable prognostic marker ( p = 0.02). However, nuclear SPP1 expression did not show any prognostic value ( p = 0.712). Our results showed a particular SPP1 prognostic relevance that is not in line with most colorectal cancer previous studies that may be attributed to the molecular pathophysiology of our colorectal cancer cohort. Saudi Arabia has both specific genomic makeup and particular environment that could lead to distinctive molecular roots of cancer. SPP1 has several isoforms, tissue localizations and molecular functions, signaling pathways, and downstream molecular functions. Therefore, a more individualized approach for CRC studies and particularly SPP1 prognosis outcomes’ assessment is highly recommended toward precision oncology.

Background Epilepsy is genetically complex but common brain disorder of the world affecting millions of people with almost of all age groups. Novel Copy number variations (CNVs) are considered as important reason for the numerous neurodevelopmental disorders along with intellectual disability and epilepsy. DNA array based studies contribute to explain a more severe clinical presentation of the disease but interoperation of many detected CNVs are still challenging. Results In order to study novel CNVs with epilepsy related genes in Saudi family with six affected and two normal individuals with several forms of epileptic seizures, intellectual disability (ID), and minor dysmorphism, we performed the high density whole genome Agilent sure print G3 Hmn CGH 2x 400 K array-CGH chips analysis. Our results showed de novo deletions, duplications and deletion plus duplication on differential chromosomal regions in the affected individuals that were not shown in the normal fathe and normal kids by using Agilent CytoGenomics 3.0.6.6 softwear. Copy number gain were observed in the chromosome 1, 16 and 22 with LCE3C, HPR, GSTT2, GSTTP2, DDT and DDTL genes respectively whereas the deletions observed in the chromosomal regions 8p23-p21 (4303127–4337759) and the potential gene in this region is CSMD1 (OMIM: 612279). Moreover, the array CGH results deletions and duplication were also validated by using primer design of deleted regions utilizing the flanked SNPs using simple PCR and also by using quantitative real time PCR. Conclusions We found some of the de novo deletions and duplication in our study in Saudi family with intellectual disability and epilepsy. Our results suggest that array-CGH should be used as a first line of genetic test for epilepsy except there is a strong indication for a monogenic syndrome. The advanced high through put array-CGH technique used in this study aim to collect the data base and to identify new mechanisms describing epileptic disorder, may help to improve the clinical management of individual cases in decreasing the burden of epilepsy in Saudi Arabia.

The Third International Genomic Medicine Conference (3rd IGMC) was organised by the Centre of Excellence in Genomic Medicine Research (CEGMR) at the King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia (KSA). This conference is a continuation of a series of meetings, which began with the first International Genomic Medicine Conference (1st IGMC, 2011) followed by the second International Genomic Medicine Conference (2nd IGMC, 2013). The 3rd IGMC meeting presented as a timely opportunity to bring scientists from across the world to gather, discuss, and exchange recent advances in the field of genomics and genetics in general as well as practical information on using these new technologies in different basic and clinical applications. The meeting undoubtedly inspired young male and female Saudi researchers, who attended the conference in large numbers, as evidenced by the oversubscribed oral and poster presentations. The conference also witnessed the launch of the first content for npj Genomic Medicine, a high quality new journal was established in partnership by CEGMR with Springer Nature and published as part of the Nature Partner Journal series. Here, we present a brief summary report of the 2-day meeting including highlights from the oral presentations, poster presentations, workshops, poster prize-winners and comments from the distinguished scientists.

Background The identification of charge clusters (runs of charged residues) in proteins and their mapping within the protein structure sequence is an important step toward a comprehensive analysis of how these particular motifs mediate, via electrostatic interactions, various molecular processes such as protein sorting, translocation, docking, orientation and binding to DNA and to other proteins. Few algorithms that specifically identify these charge clusters have been designed and described in the literature. In this study, 197 distinctive human viral proteomes were screened for the occurrence of charge clusters (CC) using a new computational approach. Results Three hundred and seventy three CC have been identified within the 2549 viral protein sequences screened. The number of protein sequences that are CC-free is 2176 (85.3 %) while 150 and 180 proteins contained positive charge (PCC) and negative charge clusters (NCC), respectively. The NCCs (211 detected) were more prevalent than PCC (162). PCC-containing proteins are significantly longer than those having NCCs (p = 2.10-16). The most prevalent virus families having PCC and NCC were Herpesviridae followed by Papillomaviridae. However, the single-strand RNA group has in average three times more NCC than PCC. According to the functional domain classification, a significant difference in distribution was observed between PCC and NCC (p = 2. 10−8) with the occurrence of NCCs being more frequent in C-terminal region while PCC more often fall within functional domains. Only 29 proteins sequences contained both NCC and PCC. Moreover, 101 NCC were conserved in 84 proteins while only 62 PCC were conserved in 60 protein sequences. To understand the mechanism by which the membrane translocation functionalities are embedded in viral proteins, we screened our PCC for sequences corresponding to cell-penetrating peptides (CPPs) using two online databases: CellPPd and CPPpred. We found that all our PCCs, having length varying from 7 to 30 amino-acids were predicted as CPPs. Experimental validation is required to improve our understanding of the role of these PCCs in viral infection process. Conclusions Screening distinctive cluster charges in viral proteomes suggested a functional role of these protein regions and might provide potential clues to improve the current understanding of viral diseases in order to tailor better preventive and therapeutic approaches. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-3086-3) contains supplementary material, which is available to authorized users.

Background Her2/neu is an oncogene that plays an important role in the pathogenesis of many cancer types. In bladder carcinoma (BC), the clinical significance of Her2/neu status remains under-investigated and poorly linked to the patients’ clinic-pathological features and survival status. Thus, the current study was conducted to assess Her2/neu status in a cohort of patients’ in Saudi Arabia, and to explore its prognostic value in BC. Methods A total of 160 consent patients of transitional cell carcinoma (TCC) of bladder were arranged on a tissue microarray (TMA) and stained by immunohistochemistry (IHC) and bright-field dual in situ hybridization (BDISH) methods. The intensity of Her2/neu protein receptor immunostaining was evaluated, correlated to Her2/neu gene amplification status in TCC and assessed for potential clinical value by correlation measures. Results IHC data demonstrated that Her2/neu protein is expressed in 60 % (2+ and 3+) of our TCC patient’s cohort from Saudi Arabia. Her2/neu gene amplification is detected in 25 % by BDISH. There was a strong association between Her2/neu protein levels and lymph node invasion (p = 0.04), tumor stage (p = 0.002), vascular invasion and borderline significance with distant metastasis (p = 0.07). Amplification of Her2/neu gene was associated with tumor grade (p = 0.03) and poor disease-specific survival (p = 0.02), in that, patients with non-amplified Her2/neu gene live longer. Interestingly, there was a reasonable concordance rate (71 %) between IHC and BDISH data in the analyzed cohort. Conclusion The study showed that 25 % of our patients’ cohort has Her2/neu over-expression. This Her2/neu (over-expression/amplification) status was concordant using either IHC or BDISH and significantly associated with disease aggressiveness and poor outcome. These findings suggested a potential impact of anti-Her2 targeted therapy in the treatment of bladder cancer with amplified/overexpressed HER2 that needs further investigation.