Expression pattern, prognostic value and potential microRNA silencing of FZD8 in breast cancer.

Breast cancer (BC) is one of the most widespread types of cancer affecting females, and therefore, early diagnosis is critical. BC is a complex heterogeneous disease affected by several key pathways. Among these, WNT proteins and their frizzled receptors (FZD) have been demonstrated to be crucial in regulating a number of cellular and molecular events in BC tumorigenesis. The role of the WNT receptor, FZD8, in BC has received minimal attention; for that reason, the present study examined the prognostic value of its protein expression pattern in a BC cohort. FZD8 cytoplasmic expression pattern analysis revealed that ~38% of the primary samples presented with a high expression profile, whereas ~63% of the samples had a low expression profile. Overall, ~46% of the malignant tissues in the lymph node-positive samples exhibited an increased FZD8 cytoplasmic expression, whereas 54% exhibited low expression levels. An increased expression of FZD8 was associated with several clinicopathological characteristics of the patients, including a low survival rate, tumor vascular invasion, tumor size and grade, and molecular subtypes. Affymetrix microarray triple-negative BC datasets were analyzed and compared with healthy breast tissues in order to predict the potential interfering microRNAs (miRNAs) in the WNT/FZD8 signaling pathway. A total of 29 miRNAs with the potential to interact with the WNT/FZD8 signaling pathway were identified, eight of which exhibited a significant prediction score. The target genes for each predicted miRNA were identified. On the whole, the findings of the present study suggest that FZD8 is a potential prognostic marker for BC, shedding some light onto the silencing mechanisms involved in the complex BC signaling.

Correlations of demographical and clinicopathological features with patient outcome of pancreatic ductal adenocarcinoma: A retrospective study (2010-2018) from a Libyan Cohort.

Objective: The aim of the study was to study the correlations of demographical and clinicopathological variables of patients with pancreatic ductal adenocarcinoma (PDAC) and evaluate the association of these variables with patients' survival outcomes. Patients and Methods: A retrospective analysis of 123 patients with PDAC were diagnosed and treated at the National Cancer Institute, Misurata, Libya during the 2010-2108 period. Data for demographics, clinicopathological, biological variables, risk factors, presentation, treatment, and survival-related data were collected from the patients' medical records. Results: The mean age of patient was 61.2 years (range: 19-90 years) and most of patients (80.5%) were aged >50 years. For gender distribution, PDAC was more frequent in males (59.3%). Abdominal pain was the most frequent presenting symptom (84.6%) and 78% (96 patients) among them had head tumors. Most patients (80.5%) presented with unresectable tumor at diagnosis. Disease-free survival was better in patients with early stage (P < 0.0001), low-grade tumor (P = 0.001), resectable tumor (P < 0.0001), and with carcinoembryonic antigen levels <5 ng/ml (P = 0.004). Multivariate Cox's regression analysis showed that tumor stage is an independent poor survival factor (P = 0.002). Age at diagnosis, gender, family history, and position of tumor did not show any significant associations with patient outcome. Conclusion: Libyan patients with PDAC had different demographics, clinicopathological, and biological variables. Typically, they presented with unresectable tumor, advanced stages, and had very short survival times. These results urge us to conduct in-depth biomolecular research studies to identify effective early diagnostics and therapeutics biomarkers in order to fight this disease before it escalates.

Current Healthcare Systems in Light of Hyperendemic NCDs and the COVID-19 Pandemic: Time to Change.

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.

Analysis of MTNR1A Genetic Polymorphisms and Their Association with the Reproductive Performance Parameters in Two Mediterranean Sheep Breeds.

Sheep farming plays an important economic role, and it contributes to the livelihoods of many rural poor in several regions worldwide and particularly in Tunisia. Therefore, the steady improvement of ewes' reproductive performance is a pressing need. The MTNR1A gene has been identified as an important candidate gene that plays a key role in sheep reproduction and its sexual inactivity. It is involved in the control of photoperiod-induced seasonality mediated by melatonin secretion. The aim of this study was to identify SNPs in the MTNR1A gene in two Tunisian breeds, Barbarine (B) and Queue Fine de l'Ouest (QFO). DNA extracted from the blood of 77 adult ewes was sequenced. Selected ewes were exposed to adult fertile rams. A total of 26 SNPs were detected; 15 SNPs in the promoter region and 11 SNPs in the exon II were observed in both (B) and (QFO) breeds. The SNP rs602330706 in exon II is a novel SNP detected for the first time only in the (B) breed. The SNPs rs430181568 and rs40738822721 (SNP18 and SNP20 in our study, respectively) were totally linked in this study and can be considered a single marker. DTL was associated with SNP18 and SNP20 in (B) ewes (p < 0.05); however, no significant difference was detected between the three genotypes (G/G, G/A, and A/A) at these two SNPs. Fertility rate and litter size parameters were not affected by SNP18 and SNP20. There was an association between these two polymorphisms and (B) lambs' birth weights (p < 0.05). Furthermore, the ewes with the A/A genotype gave birth to lambs with a higher weight compared to the other two genotypes for this breed (p < 0.05). There was not an association between SNP 18 and SNP20 and (QFO) ewes' reproductive parameters. These results might be considered in future sheep selection programs for reproductive genetic improvement.

Editorial: Advances in genomic and genetic tools, and their applications for understanding embryonic development and human diseases.

Significant advances have been recently made in the development of the genetic and genomic platforms. This has greatly contributed to a better understanding of gene expression and regulation machinery. Consequently, this led to considerable progress in unraveling evidence of the genotype-phenotype correlation between normal/abnormal embryonic development and human disease complexity. For example, advanced genomic tools such as next-generation sequencing, and microarray-based CGH have substantially helped in the identification of gene and copy number variants associated with diseases as well as in the discovery of causal gene mutations. In addition, bioinformatic analysis tools of genome annotation and comparison have greatly aided in data analysis for the interpretation of the genetic variants at the individual level. This has unlocked potential possibilities for real advances toward new therapies in personalized medicine for the targeted treatment of human diseases. However, each of these genomic and bioinformatics tools has its limitations and hence further efforts are required to implement novel approaches to overcome these limitations. It could be possible that the use of more than one platform for genotype-phenotype deep analysis is an effective approach to disentangling the cause and treatment of the disease complexities. Our research topic aimed at deciphering these complexities by shedding some light on the recent applications of the basic and advanced genetic/genomic and bioinformatics approaches. These include studying gene-gene, protein-protein, and gene-environment interactions. We, in addition, aimed at a better understanding of the link between normal/abnormal embryonic development and the cause of human disease induction.

Medicine and health of 21st Century: Not just a high biotech-driven solution.

Many biotechnological innovations have shaped the contemporary healthcare system (CHS) with significant progress to treat or cure several acute conditions and diseases of known causes (particularly infectious, trauma). Some have been successful while others have created additional health care challenges. For example, a reliance on drugs has not been a panacea to meet the challenges related to multifactorial noncommunicable diseases (NCDs)-the main health burden of the 21st century. In contrast, the advent of omics-based and big data technologies has raised global hope to predict, treat, and/or cure NCDs, effectively fight even the current COVID-19 pandemic, and improve overall healthcare outcomes. Although this digital revolution has introduced extensive changes on all aspects of contemporary society, economy, firms, job market, and healthcare management, it is facing and will face several intrinsic and extrinsic challenges, impacting precision medicine implementation, costs, possible outcomes, and managing expectations. With all of biotechnology's exciting promises, biological systems' complexity, unfortunately, continues to be underestimated since it cannot readily be compartmentalized as an independent and segregated set of problems, and therefore is, in a number of situations, not readily mimicable by the current algorithm-building proficiency tools. Although the potential of biotechnology is motivating, we should not lose sight of approaches that may not seem as glamorous but can have large impacts on the healthcare of many and across disparate population groups. A balanced approach of "omics and big data" solution in CHS along with a large scale, simpler, and suitable strategies should be defined with expectations properly managed.

Assessment of Biobanking Knowledge and Attitudes towards Biospecimen Donation among Healthcare Providers in Saudi Arabia.

BACKGROUND: Biobanking is a critical cornerstone of the global shift towards precision medicine (PM). This transformation requires smooth and informed interaction between a range of stakeholders involved in the healthcare system. In Saudi Arabia, there is still insufficient awareness of the importance of biobanking and its potential benefits for patients, the healthcare system, and society as a whole. The purpose of this study was to determine the biobanking knowledge of Saudi healthcare providers and the potential factors that might influence their self-reported attitudes toward biospecimen donation and biobanking. METHODS: A cross-sectional study was conducted targeting 636 healthcare providers in Makkah province using a structured, self-administered questionnaire. RESULTS: The study had a response rate of 61%. The mean knowledge level about biobanks was 3.5 (±1.8) out of 7. About one-third of the participants were aware of the Human Genome Project (HGP) (35%) or the term "biobank" (34%). The mean rating of their attitude was 37.3 (±4.3) out of 55. Most participants (74%) had a positive attitude toward medical research. Job position, general health, previous blood tests, knowledge of biobanking, and attitudes toward biomedical research were significantly related and predictors of willingness to donate biospecimens (p < 0.05). However, concerns about biospecimen misuse and confidentiality were the main reasons for not donating biospecimens. CONCLUSIONS: This study has shown that healthcare providers mostly lack basic knowledge about HGP and biobanks and their roles and activities, and therefore are generally disinclined to actively participate in biospecimens' collection and management. It is recommended that medical trainees receive more education and awareness about biobanks and the latest personalized healthcare approaches to improve translational research outcomes and achieve precision medicine.

Strong prognostic value of SLAMF7 protein expression in patients with lymph node-positive breast cancer.

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 (P<0.007), tumor invasion (P<0.008) 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.

Increased Glypican-3 immunostaining is associated with longer survival outcomes in colorectal carcinoma.

Glypicans (GPC) are involved in the developmental morphogenesis and regulatory processes of cell signalling. Abnormal expression has been observed in different cancer types. One hundred and thirty-seven colorectal carcinoma (CRC) and 44 nodal metastases were used to create tissue microarrays. Immunohistochemistry was done to detect and evaluate the impact of immunostaining patterns of GPC-3 protein in CRC. GPC-3 immunostaining is increased in CRC and nodal metastasis (p < 0.001) and was not association with clinicopathological parameters. GPC-3 immunostaining was associated with longer disease-free survival (p = 0.021) and overall survival (p = 0.05). For the first time, we show GPC-3 immunostaining association with survival outcomes in CRC. GPC-3 may be used as an independent prognostic factor for survival in CRC.

Prognostic value of serum CEA and CA19-9 levels in pancreatic ductal adenocarcinoma.

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 (P<0.016 and (P<0.014, log-rank, respectively) and lower disease-free survival rates (P<0.002 and P<0.0001, log-rank, respectively). The present study demonstrated significant clinical and prognostic value of serum levels of biomarkers CEA and CA19-9 for Libyan patients with PDAC. Moreover, patients with PDAC with higher serum CEA and CA19-9 levels had more aggressive tumors, higher rates of disease recurrence and shorter overall survival rates and thus required more vigilant follow-up. Further multinational studies with larger PDAC cohorts are warranted to confirm these findings in terms of improved clinical decision making, more effective management and improved survival.

Diagnostic value of risk of malignancy index in the clinical evaluation of ovarian mass.

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 (P<0.0001) 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 (P<0.0001). 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.

Infertility in Men: Advances towards a Comprehensive and Integrative Strategy for Precision Theranostics.

Male infertility is an increasing and serious medical concern, though the mechanism remains poorly understood. Impaired male reproductive function affects approximately half of infertile couples worldwide. Multiple factors related to the environment, genetics, age, and comorbidities have been associated with impaired sperm function. Present-day clinicians rely primarily on standard semen analysis to diagnose male reproductive potential and develop treatment strategies. To address sperm quality assessment bias and enhance analysis accuracy, the World Health Organization (WHO) has recommended standardized sperm testing; however, conventional diagnostic and therapeutic options for male infertility, including physical examination and semen standard analysis, remain ineffective in relieving the associated social burden. Instead, assisted reproductive techniques are becoming the primary therapeutic approach. In the post-genomic era, multiomics technologies that deeply interrogate the genome, transcriptome, proteome, and/or the epigenome, even at single-cell level, besides the breakthroughs in robotic surgery, stem cell therapy, and big data, offer promises towards solving semen quality deterioration and male factor infertility. This review highlights the complex etiology of male infertility, especially the roles of lifestyle and environmental factors, and discusses advanced technologies/methodologies used in characterizing its pathophysiology. A comprehensive combination of these innovative approaches in a global and multi-centric setting and fulfilling the suitable ethical consent could ensure optimal reproductive and developmental outcomes. These combinatorial approaches should allow for the development of diagnostic markers, molecular stratification classes, and personalized treatment strategies. Since lifestyle choices and environmental factors influence male fertility, their integration in any comprehensive approach is required for safe, proactive, cost-effective, and noninvasive precision male infertility theranostics that are affordable, accessible, and facilitate couples realizing their procreation dream.

High N-Cadherin Protein Expression in Ovarian Cancer Predicts Poor Survival and Triggers Cell Invasion.

Ovarian cancer (OC) is among the most lethal cancer among all gynaecological malignancies. Since most OC patients are diagnosed only at advanced stages mainly because of their imperceptible/nonspecific symptoms, survival rates are low. Therefore, more molecular biomarkers are needed to achieve more effective molecular stratification for better prognostic and theranostic outcomes. The cadherin family, particularly N-cadherin (N-CAD; also known as CDH2), is critical for cell-cell adhesion and epithelial- mesenchymal transition (EMT) of cancer. N-CAD protein has also been shown to be overexpressed in many advanced carcinomas. The aim of this study was to investigate the expression patterns of N-CAD protein, determine their correlations with the clinicopathological features of OC patients, and evaluate its prognostic value and involvement in EMT and metastasis. Protein expression of N-CAD was studied in 117 formalin-fixed and paraffin-embedded (FFPE) blocks from patients diagnosed with OC using Tissue Microarray and immunohistochemistry techniques. The N-CAD protein was overexpressed in 58% of our OC cohort. Furthermore, its cytoplasmic overexpression was significantly correlated with tumor grade (p= 0.05), tumor subtype (p= 0.05), tumor necrosis (p= 0.01), and age at menarche (p= 0.002). Interestingly, Kaplan-Meier analysis showed a significant correlation of disease-free survival (DFS) with OC patients with cytoplasmic N-CAD overexpression (p< 0.03, log rank). Patients with high N-CAD expression have approximately twice the recurrence rate at 5-year follow-up. The results of this study demonstrate a poor prognostic role of N-CAD overexpression in OC, which is reflected in higher recurrence and death rates of OC and its molecular contribution to EMT and distant metastasis. Therefore, OC patients with overexpressed N-CAD need to be monitored more frequently and closely. Further studies with larger patient cohorts are needed to validate these findings, demystify the role of N-CAD in OC pathophysiology, and further investigate its role as a potential therapeutic target.

Utility of Circulating Cell-Free DNA in Assessing Microsatellite Instability and Loss of Heterozygosity in Breast Cancer Using Human Identification Approach.

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.

The Prognostic Value of the Developmental Gene FZD6 in Young Saudi Breast Cancer Patients: A Biomarkers Discovery and Cancer Inducers OncoScreen Approach.

Wnt signalling receptors, Frizzleds (FZDs), play a pivotal role in many cellular events during embryonic development and cancer. Female breast cancer (BC) is currently the worldwide leading incident cancer type that cause 1 in 6 cancer-related death. FZD receptors expression in cancer was shown to be associated with tumour development and patient outcomes including recurrence and survival. FZD6 received little attention for its role in BC and hence we analysed its expression pattern in a Saudi BC cohort to assess its prognostic potential and unravel the impacted signalling pathway. Paraffin blocks from approximately 405 randomly selected BC patients aged between 25 and 70 years old were processed for tissue microarray using an automated tissue arrayer and then subjected to FZD6 immunohistochemistry staining using the Ventana platform. Besides, Ingenuity Pathway Analysis (IPA) knowledgebase was used to decipher the upstream and downstream regulators of FZD6 in BC. TargetScan and miRabel target-prediction databases were used to identify the potential microRNA to regulate FZD6 expression in BC. Results showed that 60% of the BC samples had a low expression pattern while 40% showed a higher expression level. FZD6 expression analysis showed a significant correlation with tumour invasion (p < 0.05), and borderline significance with tumour grade (p = 0.07). FZD6 expression showed a highly significant association with the BC patients' survival outcomes. This was mainly due to the overall patients' cohort where tumours with FZD6 elevated expression showed higher recurrence rates (DFS, p < 0.0001, log-rank) and shorter survival times (DSS, p < 0.02, log-rank). Interestingly, the FZD6 prognostic value was more potent in younger BC patients as compared to those with late onset of the disease. TargetScan microRNA target-prediction analysis and validated by miRabel showed that FZD6 is a potential target for a considerable number of microRNAs expressed in BC. The current study demonstrates a potential prognostic role of FZD6 expression in young BC female patients and provides a better understanding of the involved molecular silencing machinery of the Wnt/FZD6 signalling. Our results should provide a better understanding of FZD6 role in BC by adding more knowledge that should help in BC prevention and theranostics.

Detection of genetic mutations in patients with breast cancer from Saudi Arabia using Ion AmpliSeq™ Cancer Hotspot Panel v.2.0.

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® DNA Mini Kit. The isolated DNA was quantified using a Qubit™ dsDNA BR Assay Kit with a Qubit 2.0 Fluorometer. Ion semiconductor sequencing technology with an Ion S5 System and AmpliSeq™ Cancer Hotspot Panel v2 were utilized to analyze ~2,800 mutations described in the Catalogue of Somatic Mutations in Cancer from 50 oncogenes and tumor suppressor genes. Ion Reporter Software v.5.6 was used to evaluate the genomic alterations in all the samples after alignment to the hg19 human reference genome. The results showed that out of the 50 genes, 26 mutations, including 17 (65%) missense point mutations (single nucleotide variants), and 9 (35%) frameshift (insertion/deletion) mutations, were identified in 11 genes across the cohort in 61 samples (95%). Mutations were predominantly focused on two genes, PIK3CA and TP53, in the BC genomes of the sample set. PIK3CA mutation, c.1173A>G located in exon 9, was identified in 15 patients (46.9%). The TP53 mutations detected were a missense mutation (c.215C>G) in 26 patients (86.70%) and 1 frameshift mutation (c.215_216insG) in 1 patient (3.33%), located within exon 3 and 5, respectively. This study revealed specific mutation profiles for every BC patient, Thus, the results showed that Ion Torrent DNA Sequencing technology may be a possible diagnostic and prognostic method for developing personalized therapy based on the patient's individual BC genome.

Leptin Protein Expression and Promoter Methylation in Ovarian Cancer: A Strong Prognostic Value with Theranostic Promises.

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.

Prognostic value of E-Cadherin and its tumor suppressor role in Saudi women with advanced epithelial ovarian cancer.

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 < 0.0001), while borderline significant correlations were observed with both tumor grade (p = 0.06) and stage (p = 0.07). Interestingly, Kaplan-Meier survival analysis showed that OC patients with membranous E-CAD expression survived longer than those with no E-CAD expression mainly those at advanced stages (p < 0.009). Further in silico analysis confirms the key roles of E-CAD in OC molecular functions. CONCLUSION: we reported a prognosis value of membranous E-CAD in advanced stage OC patients. Further validation using larger cohorts is recommended to extract clinically relevant outcomes towards better OC management and individualized oncology.

Assessment of Knowledge and Self-Reported Use of Nutrition Facts Labels, Nutrient Content, and Health Claims among Saudi Adult Consumers.

BACKGROUND: 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.

Population genetic data for 12 X-STR loci in the Central Saudi region using investigator Argus X-12 amplification kit.

BACKGROUND: X-chromosome short tandem repeat (X-STR) markers are important in forensic identity investigations and kinship analysis. SUBJECT AND METHODS: In the current study, the distribution of 12 X-STR loci located in four linkage groups was evaluated using Investigator® Argus X-12 Amplification Kit in 200 unrelated healthy individuals (105 males and 95 females) from the central region of Saudi Arabia in order to develop an allelic frequency database for the markers included in the kit. RESULTS: DXS10146 locus was the most informative with 21 alleles, while DXS8378 locus was the least with five alleles. Forensic parameters showed that all X-STRs loci, either as individual markers or as linkage groups, provide genetic information with high discrimination that is appropriate for forensic purposes with polymorphism information content (PIC), power of exclusion (PE), and paternity index (PI) varying from 0.61211 to 0.917979, 0.38722 to 0.842949, and 0.038416 to 0.16367, respectively. The pairwise genetic distance fixation index (Fst) results showed that the Saudi population is genetically closer to the Egyptian and Emirati populations and distant to the Turkish population. CONCLUSION: The current study revealed that Investigator® Argus 12 X-STR kit would support the forensic application, kinship testing involving female offspring, and human identification in the Saudi population.