Incidence and risk factors of prostate cancer among the Northern and Eastern parts of the United Arab Emirates population.

BACKGROUND: Prostate cancer (PCa) is a prevalent disease worldwide. However, the incidence and patient-specific risk factors of PCa in the Middle East, specifically in the United Arab Emirates, have not been previously reported. METHODS: We conducted a retrospective cohort study on 2377 men diagnosed with either benign prostatic hyperplasia (BPH) or PCa in the Northern and Eastern regions of the United Arab Emirates, excluding the Western part, which includes Abu Dhabi. The study spanned from January 2012 and December 2021. To calculate the PCa incidence rate, we utilized the world age-standardized incidence rates (W-ASIR) categorized by age groups. Patient-specific risk factors of PCa were identified through a multivariate logistic regression analysis of clinical data. RESULTS: A total of 247 cases of PCa and 2130 cases of BPH were included in the study. In our cohort, the W-ASIR for PCa was 21.3 per 100,000 men. The incidence of PCa showed an increasing trend with age, with the highest incidence observed among men aged 70 years and older. Accordingly, multivariate analysis revealed that age over 70 was associated with an increased risk of PCa (OR: 2.546, 95% confidence interval [CI]: 1.892-3.425, p < 0.01). On the other hand, preexisting conditions such as hypertension and diabetes mellitus were found to lower the risk of PCa (OR: 0.222, 95% CI: 0.163-0.302, p < 0.001) and (OR: 0.364, 95% CI: 0.205-0.648, p < 0.001), respectively. Additionally, metformin intake was associated with a reduced risk of PCa (OR: 0.385, 95% CI: 0.190-0.782, p = 0.008); while insulin usage increased the risk of PCa (OR: 2.586, 95% CI: 1.539-4.344, p < 0.001). Anti-BPH medications such as phosphodiesterase inhibitors (OR: 0.223, 95% CI: 0.069-0.723, p = 0.012) or 5-α reductase (OR: 0.206, 95% CI: 0.110-0.389, p < 0.000), were found to lower the risk of PCa. CONCLUSION: The findings underscore the high incidence of PCa in the United Arab Emirates, with age being a significant factor. Furthermore, the study highlights the influence of certain comorbidities and medications on the risk of developing PCa within the United Arab Emirates population.

Epidemiological and Clinical Characteristics Associated with COVID-19 Severity Among Hospitalized Patients in the United Arab Emirates: A Retrospective Multicentre Study.

OBJECTIVES: To investigate the clinical and epidemiological factors associated with severe COVID-19 cases in hospitalized patients across two emirates within the United Arab Emirates (UAE). METHODS: A retrospective observational analytical study analysed data from 738 medical records and conducted 573 in-depth interviews with patients hospitalized across multiple healthcare centers in the UAE, between 29 January 2020 and 14 October 2021. Regression analysis predicted risk factors for COVID-19 severity. RESULTS: Main risk factors identified were crowding (aOR 1.919; 95%CI 1.144, 3.221), obesity (aOR 2.383; 95%CI 1.332, 4.263), diabetes (aOR 11.14; 95%CI 2.653-46.797), severe dehydration (aOR 3.219; 95%CI 2.161, 4.795), cough or sore throat (aOR 1.607; 95%CI 1.032, 2.502), shortness of breath (aOR 1.921; 95%CI 1.294, 2.853), increased days from symptom onset to admission (aOR 1.055; 95%CI 1.006, 1.105), elevated ANC (aOR 1.263, 95%CI 1.121, 1.424), and AST/SGOT (aOR 1.055, 95% CI 1.016, 1.095). Protective factors included smoking (aOR 0.367; 95%CI 0.182, 0.740), first dose of COVID-19 vaccination (aOR 0.595; 95%CI 0.377, 0.93), higher oxygen saturation (aOR 0.853; 95%CI: 0.801, 0.907) and elevated ALC (aOR 0.540; 95%CI 0.323, 0.905). CONCLUSION: Identifying risk factors is crucial for high-risk individuals who may require closer monitoring to improve their outcomes. This can provide guidance for surveillance systems and early detection strategies to mitigate the impact of future outbreaks.

Association Between Expression of Vitamin D Receptor and Insulin-Like Growth Factor 1 Receptor Among Breast Cancer Patients.

Background: Vitamin D receptor (VDR) and insulin-like growth factor 1 receptor (IGF1R) are known to be involved in breast cancer (BC) progression. Our previous work reported a correlation of differential localization of IGF1R with hormone receptor status in BC. A recent report described VDR and IGF1R as potential indicators of BC prognosis, but their interplay was not discussed. The present study focused on understanding the association of VDR expression with IGF1R activation, different molecular markers, and subtypes of BC. Methods: A retrospective study was designed to evaluate the VDR expression among 48 BC patients pathologically diagnosed as invasive BC and were surgically treated at Sharjah Breast Care Center, University Hospital Sharjah (UHS), United Arab Emirates (UAE). Formalin-fixed paraffin-embedded (FFPE) tumor blocks with appropriate clinicopathological data were subjected to immunohistochemistry (IHC), and VDR protein expression was interpreted based on the staining intensity (SI) and the percentage of the positively stained cells (PP). Results: Nearly 44% of cases in the study were vitamin D deficient. A positive VDR expression with strong intensity (score > 4) was seen in 27 cases (56.3%). The expression pattern for VDR was equally distributed in cytoplasm and nucleus. For the IGF1R intensity, 24 cases (50%) of total cohort showed strong expression. A significant association was detected between IGF1R and VDR expression (P = 0.031). Conclusions: The present study identified positive association between IGF1R and VDR expression where most of the cases with strong VDR expression displayed strong IGF1R expression. These findings may contribute to current understanding on the role of VDR in BC and its interaction with IGF1R.

Risks of prostate cancer and mortality in the city of Sharjah, United Arab Emirates.

Background: Prostatic hyperplasia (BPH) and prostate cancer (PCa) are common age-related diseases in men. According to World Health Organization (WHO), PCa is the second most common cancer among Emirati men. This study aimed to identify the risk factors associated with PCa and mortality in a cohort diagnosed with PCa between 2012 and 2021 in Sharjah, United Arab Emirates (UAE). Methods: The data collected in this retrospective case-control study included patient demographics and comorbidities, as well as PCa markers such as prostate-specific antigen (PSA), prostate volume, prostate-specific antigen density (PSAD), and Gleason scores. Risk factors for PCa were assessed using multivariate logistic regression analysis, and factors associated with all-cause mortality in PCa patients were evaluated using Cox-proportional hazard analysis. Results: Of the 192 cases analyzed in this study, 88 were diagnosed with PCa and 104 were diagnosed with BPH. Regarding risk factors for PCa, a higher risk of PCa was associated with age 65 or older (OR=2.76, 95% confidence interval (CI): 1.04-7.30; P=0.038) and serum PSAD greater than 0.1 ng/mL2 (OR=3.48, 95% CI:1.66-7.32; P=0.001), whereas being of UAE nationals (OR=0.40, 95% CI:0.18-0.88; P=0.029) were associated with lower risk of PCa, after adjusting for patient demographics and comorbidities. Moreover, regarding cancer markers, higher serum PSA level (P=0.003) and smaller prostate volume (P=0.028) were associated with a higher risk of PCa, after adjusting with patients' age and BMI. Additionally, a high-grade Gleason score was associated with an increased risk of all-cause mortality after adjusting for patient's age and BMI (hazard ratio, aHR= 2.3, 95% CI:1.3-4.1; P= 0.016). Conclusion: This study found that age 65 or older and serum PSAD greater than 0.1 ng/mL2 are risk factors for PCa, while UAE nationality is associated with a lower risk. PSAD may be a better screening marker for PCa compared to traditional markers such as PSA and prostate volume.

Thyroid cancer incidence in the United Arab Emirates: a retrospective study on association with age and gender.

Background: Thyroid cancer is the ninth most common malignancy worldwide, but the third most common malignancy in the United Arab Emirates (UAE) . To our knowledge, this is the first UAE nationwide study aimed at presenting incidence rates of thyroid cancer at the national level of UAE based upon data from the national cancer registry and GLOBOCAN. Methods: Between 2011 and 2017, a total of 2036 thyroid cancer cases from UAE patients were registered, of which 75.3% were female and 24.7% male patients. Results: The results showed 6.6% increase in thyroid cancer cases in the UAE from 2011 to 2017 (p < 0.001) with a rise of approximately 400 cases per year from 2011 to 2040. Age standardized rate calculations showed increase in prevalence from 1.18 in 2011 to 4.32 in 2017 but decreases in incidence from 1.05 in 2011 to 0.15 in 2017. This trend is confirmed by the predictive model showing increase in incidence from 0.15 in 2017 to 0.64 by 2040. Gender was shown to be significantly associated with thyroid cancer. The female to male ratio was significantly higher in Emirati patients (4.86:1) (p < 0.001) than expat patients (2.47:1) (p < 0.01). Interestingly, expat patients contributed to the majority of thyroid cancer cases despite having lower female to male ratio. The age at diagnosis was significantly associated with thyroid cancer (p = 0.03) with the highest frequency diagnosed at 35-39 years of age. Globally, data from the predictive model showed that Asia had the highest rate of increase per year and UAE the lowest. Conclusions: The slight increase in thyroid cancer prevalence and incidence, together with the different female to male ratio and diagnosis at younger age warrants further investigation at the molecular level from UAE thyroid cancer patients to elucidate the molecular basis of thyroid cancer.

In silico Analysis of Publicly Available Transcriptomics Data Identifies Putative Prognostic and Therapeutic Molecular Targets for Papillary Thyroid Carcinoma.

Background: Thyroid cancer is the most common endocrine malignancy. However, the molecular mechanism involved in its pathogenesis is not well characterized. Purpose: The objective of this study is to identify key cellular pathways and differentially expressed genes along the thyroid cancer pathogenesis sequence as well as to identify potential prognostic and therapeutic targets. Methods: Publicly available transcriptomics data comprising a total of 95 samples consisting of 41 normal, 28 non-aggressive and 26 metastatic papillary thyroid carcinoma (PTC) cases were used. Transcriptomics data were normalized and filtered identifying 9394 differentially expressed genes. The genes identified were subjected to pathway analysis using absGSEA identifying PTC related pathways. Three of the genes identified were validated on 508 thyroid cancer biopsies using RNAseq and TNMplot. Results: Pathway analysis revealed a total of 2193 differential pathways among non-aggressive samples and 1969 among metastatic samples compared to normal tissue. Pathways for non-aggressive PTC include calcium and potassium ion transport, hormone signaling, protein tyrosine phosphatase activity and protein tyrosine kinase activity. Metastatic pathways include growth, apoptosis, activation of MAPK and regulation of serine threonine kinase activity. Genes for non-aggressive are KCNQ1, CACNA1D, KCNN4, BCL2, and PTK2B and metastatic PTC are EGFR, PTK2B, KCNN4 and BCL2. Three of the genes identified were validated using clinical biopsies showing significant overexpression in aggressive compared to non-aggressive PTC; EGFR (p < 0.05), KCNN4 (p < 0.001) and PTK2B (p < 0.001). DrugBank database search identified several FDA approved drug targets including anti-EGFR Vandetanib used to treat thyroid cancer in addition to others that may prove useful in treating PTC. Conclusion: Transcriptomics analysis identified putative prognostic targets including EGFR, PTK2B, BCL2, KCNQ1, KCNN4 and CACNA1D. EGFR, PTK2B and KCN44 were validated using thyroid cancer clinical biopsies. The drug search identified FDA approved drugs including Vandetanib in addition to others that may prove useful in treating the disease.

Unilateral Biportal Endoscopic Tumor Removal and Percutaneous Stabilization for Extradural Tumors: Technical Case Report and Literature Review.

Background: Extradural spinal tumors arise from soft or bony tissues in the spine and account for majority of spinal tumors. Interest in the unilateral biportal endoscopic (UBE) technique is rising, because it can easily decompress the bony spinal canal and accommodate all open surgical instruments under endoscopic guidance. However, reports of this technique have been limited to certain diseases. This study first demonstrates the UBE technique for extradural tumor biopsy and removal, and percutaneous stabilization in a 72-year-old female patient with dramatic symptom improvement. Methods: We used the UBE technique for decompression and the percutaneous screw fixation technique for stabilization in a patient with an extradural mass compressing the thecal sac and destroying the posterior element. Under endoscopic guidance, a unilateral approach was used, and decompression and flavectomy were performed bilaterally. After decompression, tumor removal and biopsy were performed using various forceps and biopsy needles. After confirming sufficient spinal canal decompression, the screw was placed percutaneously. We evaluated the technical process of the procedure, the patient's pre- and postoperative pain (using the visual analog scale), and operative radiology and pathologic results. Results: Postoperative pain and disability improved clinically, and spinal alignment stabilized radiologically. As the pathology findings confirmed an aneurysmal bone cyst, the treatment was completed without adjuvant therapy. Conclusions: We treated an unstable spine due to an extradural tumor with the UBE and percutaneous screw techniques.

Transcriptomic Changes Associated with ERBB2 Overexpression in Colorectal Cancer Implicate a Potential Role of the Wnt Signaling Pathway in Tumorigenesis.

Colorectal cancer (CRC) remains the third most common cause of cancer mortality worldwide. Precision medicine using OMICs guided by transcriptomic profiling has improved disease diagnosis and prognosis by identifying many CRC targets. One such target that has been actively pursued is an erbb2 receptor tyrosine kinase 2 (ERBB2) (Human Epidermal Growth Factor Receptor 2 (HER2)), which is overexpressed in around 3-5% of patients with CRC worldwide. Despite targeted therapies against HER2 showing significant improvement in disease outcomes in multiple clinical trials, to date, no HER2-based treatment has been clinically approved for CRC. In this study we performed whole transcriptome ribonucleic acid (RNA) sequencing on 11 HER2+ and 3 HER2- CRC patients with advanced stages II, III and IV of the disease. In addition, transcriptomic profiling was carried out on CRC cell lines (HCT116 and HT29) and normal colon cell lines (CCD841 and CCD33), ectopically overexpressing ERBB2. Our analysis revealed transcriptomic changes involving many genes in both CRC cell lines overexpressing ERBB2 and in HER2+ patients, compared to normal colon cell lines and HER2- patients, respectively. Gene Set Enrichment Analysis indicated a role for HER2 in regulating CRC pathogenesis, with Wnt/ß-catenin signaling being mediated via a HER2-dependent regulatory pathway impacting expression of the homeobox gene NK2 homeobox 5 (NKX2-5). Results from this study thus identified putative targets that are co-expressed with HER2 in CRC warranting further investigation into their role in CRC pathogenesis.

Expression of immune checkpoints (PD-L1 and IDO) and tumour-infiltrating lymphocytes in breast cancer.

Background: Breast cancer (BC) has become the most common cancer globally in 2020 as well as in the United Arab Emirates. The breast tumor microenvironment is composed of various immune cell types, including lymphocytes. Tumour-infiltrating lymphocytes (TILs) play a crucial role in tumor eradication and progression. Further, immune checkpoint markers such as programmed death receptor ligand 1 (PD-L1) and indoleamine-2,3-dioxygenase (IDO) have been associated with tumor evasion from the immune system. In this study, we aimed to explore the status of TILs, PD-L1 and IDO as well as to investigate their association with the clinicopathological parameters. Materials and methods: A total of 59 patients diagnosed with primary infiltrating BC were selected, after which tissue sections were stained to identify TILs along with immunohistochemical staining of PD-L1 and IDO. Moreover, in-silico tools were used to assess the expression of PD-L1, IDO and CD3ε in various molecular subtypes of BC. Results: It was found that the percentage of TILs correlated with estrogen receptor (ER) and progesterone receptor (PR) expression. This was supported by the finding that most of the triple-negative breast cancer (TNBC) cases belonged to the group with a high percentage of TILs (h-TILs). Similarly, the expression of PD-L1 and IDO was correlated with the ER and PR, whereas TNBC cases showed a high expression of PD-L1 and IDO. This goes in line with the in-silico findings where the TNBC group showed the highest expression of PD-L1 and IDO as well as the T cell marker CD3ε. Conclusion: This study highlighted a possible link between the immunosuppressive markers PD-L1 and IDO with TILs density in the BC microenvironment.

Ferritin, blood urea nitrogen, and high chest CT score determines ICU admission in COVID-19 positive UAE patients: A single center retrospective study.

Coronavirus Disease (COVID-19) was declared a pandemic by WHO in March 2020. Since then, additional novel coronavirus variants have emerged challenging the current healthcare system worldwide. There is an increased need for hospital care, especially intensive care unit (ICU), for the patients severely affected by the disease. Most of the studies analyzed COVID-19 infected patients in the hospitals and established the positive correlation between clinical parameters such as high levels of D-dimer, C-reactive protein, and ferritin to the severity of infection. However, little is known about the course of the ICU admission. The retrospective study carried out at University Hospital Sharjah, UAE presented here reports an integrated analysis of the biochemical and radiological factors among the newly admitted COVID-19 patients to decide on their ICU admission. The descriptive statistical analysis revealed that patients with clinical presentations such as acute respiratory distress syndrome (ARDS) (p<0.0001) at the time of admission needed intensive care. The ROC plot indicated that radiological factors including high chest CT scores (>CO-RADS 4) in combination with biochemical parameters such as higher levels of blood urea nitrogen (>6.7 mg/dL;66% sensitivity and 75.8% specificity) and ferritin (>290 µg/mL, 71.4% sensitivity and 77.8% specificity) may predict ICU admission with 94.2% accuracy among COVID-19 patients. Collectively, these findings would benefit the hospitals to predict the ICU admission amongst COVID-19 infected patients.

Determinants of healthcare workers perceptions, acceptance and choice of COVID-19 vaccines: a cross-sectional study from the United Arab Emirates.

Acceptance of COVID-19 vaccine among health-care workers (HCWs) is crucial for controlling the pandemic and ensuring HCW and patient safety. Information on the acceptance of different COVID-19 vaccines is lacking. Despite the United Arab Emirates (UAE) having vaccinated most of its population, vaccine acceptance still raises concerns. This study explores COVID-19 vaccine acceptance, vaccine choice, and associated factors among HCWs in the UAE. An online national cross-sectional study was conducted among 517 HCWs. Acceptance and choice of COVID-19 vaccines were assessed, and logistic regression analysis identified predictors for vaccine acceptance. More than half (58%) of HCWs were willing to take the vaccine and give it to their family. Reasons for taking the vaccine were concerns for families contracting COVID-19 (67%) and social responsibility (64%). Reasons for refusals included concerns with side-effects (61%). Most HCWs knew of the Pfizer (79%) and Sinopharm (57%) vaccines; however, acceptance was higher for Pfizer (35%) and AstraZeneca (21%) vaccines. Being male and being influenza vaccinated predicted willingness to take the vaccine (aOR: 2.34; 95% CI:1.34-4.08; p ≤ 0.001) and (aOR: 2.13; 95% CI: 1.29-3.51; p ≤ 0.001), respectively. HCWs who expressed concerns with inadequate safety data were less likely to take the vaccine (aOR: 0.17; 95% CI: 0.10-0.30; p ≤ 0.001). Additionally, side effects, perception of risk, and level of trust of company and country of manufacture predicted acceptance and choice of vaccines. Effective vaccine policy campaigns to improve acceptance should target HCW's knowledge and awareness of perceived risks of COVID-19, safety data, social responsibility, and individual preferences for vaccine choice.

Peripheral blood cell anomalies in COVID-19 patients in the United Arab Emirates: A single-centered study.

Introduction: In this study, we aimed at exploring the morphologic and quantitative abnormalities in the peripheral blood counts of coronavirus disease 2019 (COVID-19) patients. Methods: A cohort of 131 COVID-19 patients was recruited at University Hospital Sharjah (UHS), UAE. Their peripheral blood smears were examined for morphological evaluation. Also, their clinical laboratory investigations and radiological findings were retrieved from the medical records. Our cohort consisted of 63 males and 68 females with an age of 63.6 ± 18.6 years. Results: The presence of atypical lymphocytes was observed in around 80% of the recruited COVID-19 patients. Further, monocytes with toxic cytoplasmic vacuoles were identified in 55% of the cases. Neutrophil-associated changes, including pseudo-Pelger-Huët, bands, and long nuclear endoplasm, were reported in around 25-35% of the patients. RBCs associated changes such as microcytic and hypochromic RBCs, as well as targetoid, dacrocytes, ovalocytes, echinocytes/burr cells, and schistocytes, were described. According to disease severity, RBCs chromicity was found to be significantly different between stable and critical patients. COVID-19 patients with CO-RADS 5 showed a similar change in RBCs as well as a decrease in the neutrophils with hypogranular cytoplasm. Conclusion: Peripheral blood smear assessment in COVID-19 patients could provide information about the disease state and pulmonary involvement.

Molecular Examination of Differentially Expressed Genes in the Brains of Experimental Autoimmune Encephalomyelitis Mice Post Herceptin Treatment.

OBJECTIVE: Herceptin (trastuzumab) is an approved drug for treating HER2+ breast cancer patients, but its use for other diseases is not established. We sought to investigate the effects of Herceptin on ameliorating experimental autoimmune encephalomyelitis (EAE) and to examine its effects on the expression of various genes. METHODS: We used in-silico analysis of publicly available data, qRT-PCR, and immunohistochemistry (IHC) to determine the expression of HER2+ cells in the brains of EAE mice. IHC was also utilized to determine the anti-inflammatory effects of Herceptin. The ability of Herceptin to alleviate the EAE clinical score was measured in these mice. Bioinformatics analysis of publicly available data and qRT-PCR were performed to investigate the differentially expressed genes that were either up-regulated or down-regulated during the high clinical score (HCS) of the disease. RESULTS: We observed that HER2/Erbb2, the receptor for Herceptin is upregulated in the brains of EAE mice when the brains were examined at the HCS stage. Further, we demonstrated that Herceptin ameliorates the EAE disease, increasing re-myelination, reducing brain inflammation, CD3+ T cell accumulation, and HER2+ cells in the brains of these mice. Molecular analysis demonstrated the expression of different genes that were either up-regulated or down-regulated during the HCS of the disease. Our combined bioinformatics and qRT-PCR analyses show increased mRNA expression of Atp6v0d2, C3, C3ar1, Ccl3, Ccl6, Cd74, Clec7a, Cybb, H2-Aa, Hspb1, Lilr4b, Lilrb4a, Mpeg1, Ms4a4a, Ms4a6c, Saa3, Serpina3n and Timp1, at HCS. Except for the mRNA levels of Cd74 and Clec7a which were increased at HCS when Herceptin was used in both prophylactic and therapeutic regimens, the levels of other described mRNAs were reduced. CONCLUSION: These novel findings show that Herceptin ameliorates the clinical score in EAE mice and are the first to investigate in detail the differential gene expression post-treatment with the drug.

Psychological Distress and Anxiety Levels Among Health Care Workers at the Height of the COVID-19 Pandemic in the United Arab Emirates.

Objectives: Providing medical care during a global pandemic exposes healthcare workers (HCW) to a high level of risk, causing anxiety and stress. This study aimed to assess the prevalence of anxiety and psychological distress among HCWs during COVID-19. Methods: We invited HCWs from 3 hospitals across the United Arab Emirates (UAE) to participate in an anonymous online survey between April 19-May 3, 2020. The GAD-7 and K10 measures were used to assess anxiety and psychological distress. Logistic regression models assessed associations between knowledge, attitude, worry, and levels of anxiety and psychological distress. Results: A total of 481 HCWs participated in this study. The majority of HCWs were female (73.6%) and aged 25-34 years (52.6%). More than half were nurses (55.7%) and had good knowledge of COVID-19 (86.3%). Over a third (37%) of HCWs reported moderate/severe psychological distress in the K10 measure and moderate/severe anxiety (32.3%) in the GAD-7, with frontline workers significantly reporting higher levels of anxiety (36%). Knowledge of COVID-19 did not predict anxiety and psychological distress, however, HCWs who believed COVID-19 was difficult to treat and those who perceived they were at high risk of infection had worse mental health outcomes. Worry about spreading COVID-19 to family, being isolated, contracting COVID-19 and feeling stigmatized had 1.8- to 2.5-fold increased odds of symptoms of mental health problems. Additionally, HCWs who felt the need for psychological support through their workplace showed increased odds of psychological distress. Conclusion: HCWs in the UAE reported a high prevalence of psychological distress and anxiety while responding to the challenges of COVID-19. The findings from this study emphasize the public, emotional and mental health burden of COVID-19 and highlight the importance for health systems to implement, monitor, and update preventive policies to protect HCWs from contracting the virus while also providing psychological support in the workplace.

HER2 overexpression is a putative diagnostic and prognostic biomarker for late-stage colorectal cancer in North African patients.

Aim: Colorectal cancer (CRC) is one of the leading cancers in the world. Even though its mortality and pathophysiology are well documented in the US and the European countries, it is seldom studied in North African population. Recent studies have shown link of HER2 overexpression in oesophageal and gastric cancers. The aim of this study is to assess the HER2 protein and mRNA expression and its correlation with tumor pathogenesis in Libyan CRC patients.Methodology: A total of 17 FFPE tissue blocks were collected from patients with primary CRC. The HER2 protein expression was assessed by immunohistochemistry and the mRNA expression was assessed using qRT-PCR. Survival analysis of the role of HER2 overexpression on rectal adenocarcinoma was carried out on additional 165 patients.Results: From the CRC cohort, adenocarcinoma was found to be more frequent accounting for 88.2%, and 11.8% for mucinous adenocarcinomas. Almost 47% of the cases were positive for HER2 (score ≥ 2+) and about 50% adenocarcinoma cases with tumor grade II were positive for HER2. Moreover, 57.4% adenocarcinoma patients with grade-II tumor had undergone right hemicolectomy. Furthermore, significant correlation (p = 0.03) between the HER2 mRNA expression with the tumor grade was observed. In addition, poor overall all survival was observed with high HER2 expression in rectum adenocarcinoma.Conclusion: To our knowledge, this is the first study that HER2 overexpression correlates with more aggressive colorectal cancer in North African population. Our study shows that HER2 overexpression associates with right colon surgeries. Also, the correlation of mRNA and protein expression could warrant the implementation of a nationwide screening program for HER2 positivity in CRC patients. Taken together, stratifying patients according to HER2 expression can help in the diagnosis and prognosis of CRC patients from North African origin.

Immunohistochemical Assessment of TNFAIP3/A20 Expression Correlates With Early Tumorigenesis in Breast Cancer.

BACKGROUND/AIM: Limited data exist on the expression pattern of TNFAIP3/A20, as assayed by immunohistochemistry (IHC), in breast cancer tissues. This study aimed to assess A20 expression pattern in breast cancer. MATERIALS AND METHODS: The expression of A20 was analysed using IHC in 50 breast cancer cases retrieved from the Sharjah Breast Cancer Center at the University Hospital Sharjah, United Arab Emirates. Omics survival data were also used to analyse its association with survival in endocrine-treated subgroups. RESULTS: A20 expression in breast cancer tissues was 'tumor-specific', and as compared to normal tissue areas, its expression was associated with both intensity and extent in early grade 1 (p<0.0001) in all molecular subtypes. In addition, using omics survival data from a cohort of 3,520 breast cancer patients, we showed that A20 overexpression associated with lower overall survival rate in the endocrine treated subgroups [hazard ratio (HR)=2.14, 95%CI=1.61-2.82, p<0.0001]. CONCLUSION: A20 can serve as a biomarker for early diagnosis of breast cancers.

MMP-9 (gelatinase B) expression is associated with disease-free survival and disease-specific survival in colorectal cancer patients.

Extracellular matrix degradation is required for invasion and metastasis formation in colorectal carcinoma (CRC), therefore, we have examined matrix metalloproteinases MMP-9 expression in tumors from patients with CRC. The study comprises of 360 patients who underwent bowel resection for stage II, III, IV tumors. Paraffin-embedded CRC tissue samples were used for immunohistochemical staining. Negative MMP-9 expression levels correlated with longer survival time as evaluated by disease-free survival and disease-specific survival (p =.023, p =.006). In multivariate survival (Cox) analysis, MMP9 was a significant independent predictor of DFS (p =.014), but not of DSS, which was independently predicted by disease recurrence, stage and localization. The detection of MMP-9 expression may be valuable in finding patients who are at high risk of developing disease recurrence.

Correlation of Insulin-like Growth Factor 1 Receptor Expression With Different Molecular Subtypes of Breast Cancer in the UAE.

BACKGROUND: Insulin-like growth factor 1 receptor (IGF1R) activation triggers multiple signaling pathways involved in proliferation and anti-apoptosis in breast cancer (BC). MATERIALS AND METHODS: Immunohistochemistry for IGF1R was performed on 50 BC cases; expression was assessed for staining intensity and localization pattern (mixed, membranous, and cytoplasmic) which was correlated to hormone receptor status. RESULTS: Of estrogen receptor-positive (ER+) cases, 97.2% were IGF1R+ (48.6% mixed, 43.2% membranous, and 5.4% cytoplasmic pattern) compared to ER- cases (38.5%, 7.7% and 30.8%, respectively) (p=0.003). In progesterone receptor-positive (PR+) cases, 97.2% were IGF1R+, (47.2%, 41.7% and 8.3%, respectively) compared to PR- ones (42.9%, 14.3% and 21.4%, respectively) (p=0.036). For human epidermal growth factor receptor 2-negative (HER2-) cases, 88.8% were IGF1R+ (44.4%, 8.3% and 36.1%, respectively). All HER2+ cases were IGF1R+ (71.4%, 7.1% and 21.4%, respectively) (p=0.015). In conclusion, hormone receptor-positive HER2- cases showed membranous and mixed IGF1R localization. However, hormone receptor-negative and HER2+ showed cytoplasmic or diminished IGF1R expression. CONCLUSION: These luminal subtypes may benefit from targeted IGFR therapy in the future.

Systems Immunology Analysis Reveals an Immunomodulatory Effect of Snail-p53 Binding on Neutrophil- and T Cell-Mediated Immunity in KRAS Mutant Non-Small Cell Lung Cancer.

Immunomodulation and chronic inflammation are important mechanisms utilized by cancer cells to evade the immune defense and promote tumor progression. Therefore, various efforts were focused on the development of approaches to reprogram the immune response to increase the immune detection of cancer cells and enhance patient response to various types of therapy. A number of regulatory proteins were investigated and proposed as potential targets for immunomodulatory therapeutic approaches including p53 and Snail. In this study, we investigated the immunomodulatory effect of disrupting Snail-p53 binding induced by the oncogenic KRAS to suppress p53 signaling. We analyzed the transcriptomic profile mediated by Snail-p53 binding inhibitor GN25 in non-small cell lung cancer cells (A549) using Next generation whole RNA-sequencing. Notably, we observed a significant enrichment in transcripts involved in immune response pathways especially those contributing to neutrophil (IL8) and T-cell mediated immunity (BCL6, and CD81). Moreover, transcripts associated with NF-κB signaling were also enriched which may play an important role in the immunomodulatory effect of Snail-p53 binding. Further analysis revealed that the immune expression signature of GN25 overlaps with the signature of other therapeutic compounds known to exhibit immunomodulatory effects validating the immunomodulatory potential of targeting Snail-p53 binding. The effects of GN25 on the immune response pathways suggest that targeting Snail-p53 binding might be a potentially effective therapeutic strategy.

Incidence and Clinicopathological Features of Breast Cancer in the Northern Emirates: Experience from Sharjah Breast Care Center.

BACKGROUND: Breast cancer is the most frequently reported cancer among women in the Middle East and North Africa (MENA) region. However, the available data about women breast cancer from the MENA and particularly from the Northern Emirates region of the United Arab Emirates (UAE) are scarce and inconsistent. Therefore, this study estimated the incidence, patient-specific factors including 25(OH)D levels, and clinicopathological features of breast cancer in women from the Northern Emirates. METHODS: We conducted this retrospective case-control study on 1,048 women who were referred to the Sharjah Breast Care Centre at University Hospital Sharjah between March 2016 and July 2018. Multivariate logistic regression was used for the statistical analysis of clinical data. RESULTS: Out of 1048 women with breast-related conditions referred to our canter, 94 (10%) were diagnosed with breast cancer (1 in 11), and approximately 1 in 5 of these women was younger than 40 years. After adjusting for age, body mass index and menopause status, women with serum 25-hydroxyvitamin D [25(OH)D] levels lower than 20 ng/mL were found to be at higher risk of breast cancer (odd ratio, 4.63; 95% CI, 2.61-8.23). The majority of breast cancer cases had invasive-ductal carcinoma with hormone-positive receptor molecular subtype (78 cases out of 94, 83%). HER2 overexpressing tumor (3+ by immunohistochemistry (IHC) or by fluorescence in situ hybridization (FISH)) was seen more in women younger than 40 years as compared to older women (7 cases out of 19 HER2 expressed tumors, p=0.007). CONCLUSION: Our study cohort showed a mean age of diagnosis of breast cancer in women a decade earlier than in the developed countries. Furthermore, women with breast cancer tend to be serum 25(OH)D deficient at diagnosis and to have luminal A tumors.