Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma

Background: Squamous cell carcinoma of the oral cavity (OSCC) is a common cancer form with relatively low 5-year survival rates, due partially to late detection and lack of complementary molecular markers as targets for treatment. Molecular profiling of head and neck cancer has revealed biological similarities with basal-like breast and lung carcinoma. Recently, we showed that 16 genes were consistently altered in invasive breast tumors displaying varying degrees of aggressiveness. Methods: To extend our findings from breast cancer to another cancer type with similar characteristics, we performed an integrative analysis of transcriptomic and proteomic data to evaluate the prognostic significance of the 16 putative breast cancer-related biomarkers in OSCC using independent microarray datasets and immunohistochemistry. Predictive models for disease-specific (DSS) and/or overall survival (OS) were calculated for each marker using Cox proportional hazards models. Results: We found that CBX2, SCUBE2, and STK32B protein expression were associated with important clinicopathological features for OSCC (peritumoral inflammatory infiltration, metastatic spread to the cervical lymph nodes, and tumor size). Consequently, SCUBE2 and STK32B are involved in the hedgehog signaling pathway which plays a pivotal role in metastasis and angiogenesis in cancer. In addition, CNTNAP2 and S100A8 protein expression were correlated with DSS and OS, respectively. Conclusions: Taken together, these candidates and the hedgehog signaling pathway may be putative targets for drug development and clinical management of OSCC patients

Socioeconomic - related inequalities in overweight and obesity: findings from the PERSIAN cohort study

BackgroundOverweight and obesity are major health concerns worldwide, with adverse health consequences during the life span. This study measured socioeconomic inequality in overweight and obesity among Iranian adults.MethodsData were extracted from 129,257 Iranian adults (aged 35years and older) participated in the Prospective Epidemiologic Research Studies in IrAN (PERSIAN) in 14 provinces of Iran in 2014. Socioeconomic-related inequality in overweight and obesity was estimated using the Concentration Index (C-n). The C-n further decomposed to find factors explaining the variability within the Socioeconomic related inequality in overweight and obesity.ResultsOf the total number of participants, 1.98, 26.82, 40.76 and 30.43% had underweight, normal weight, overweight and obesity respectively. The age-and sex standardized prevalence of obesity was higher in females than males (39.85% vs 18.79%). People with high socioeconomic status (SES) had a 39 and 15% higher chance of being overweight and obese than low SES people, respectively. The positive value of C-n suggested a higher concentration of overweight (0.081, 95% confidence interval [CI]; 0.074-0.087) and obesity (0.027, 95% CI; 0.021-0.034) among groups with high SES. There was a wide variation in socioeconomic-related inequality in overweight and obesity rate across 14 provinces. The decomposition results suggested that SES factor itself explained 66.77 and 89.07% of the observed socioeconomic inequalities in overweight and obesity among Iranian adults respectively. Following SES, province of residence, physical activity, using hookah and smoking were the major contributors to the concentration of overweight and obesity among the rich.ConclusionsOverall, we found that overweight and obesity is concentrated among high SES people in the study population. . Accordingly, it seems that intersectional actions should be taken to control and prevent overweight and obesity among higher socioeconomic groups. Keywords:Socioeconomic Factors; Inequality; Concentration index; overweight and obesity; PERSIAN; Ira

The COVID-19 pandemic and healthcare utilization in Iran: evidence from an interrupted time series analysis

Objectives This study aimed to examine the effect of the coronavirus disease 2019 (COVID-19) outbreak on the hospitalization rate, emergency department (ED) visits, and outpatient clinic visits in western Iran. Methods We collected data on the monthly hospitalization rate, rate of patients referred to the ED, and rate of patients referred to outpatient clinics for a period of 40 months (23 months before and 17 months after the COVID-19 outbreak in Iran) from all 7 public hospitals in the city of Kermanshah. An interrupted time series analysis was conducted to examine the impact of COVID-19 on the outcome variables in this study. Results A statistically significant decrease of 38.11 hospitalizations per 10,000 population (95% confidence interval [CI], 24.93–51.29) was observed in the first month of the COVID-19 outbreak. The corresponding reductions in ED visits and outpatient visits per 10,000 population were 191.65 (95% CI, 166.63–216.66) and 168.57 (95% CI, 126.41–210.73), respectively. After the initial reduction, significant monthly increases in the hospitalization rate (an increase of 1.81 per 10,000 population), ED visits (an increase of 2.16 per 10,000 population), and outpatient clinic visits (an increase of 5.77 per 10,000 population) were observed during the COVID-19 pandemic. Conclusion Our study showed that the utilization of outpatient and inpatient services in hospitals and clinics significantly declined after the COVID-19 outbreak, and use of these services did not return to pre-outbreak levels as of June 2021

Decomposing socioeconomic inequality in poor mental health among Iranian adult population: results from the PERSIAN cohort study

Background Socioeconomic inequality in mental health in Iran is poorly understood. This study aimed to assess socioeconomic inequality in poor mental health among Iranian adults. Methods The study used the baseline data of PERSIAN cohort study including 131,813 participants from 17 geographically distinct areas of Iran. The Erreygers Concentration index (E) was used to quantify the socioeconomic inequalities in poor mental health. Moreover, we decomposed the E to identify factors contributing to the observed socioeconomic inequality in poor mental health in Iran. Results The estimated E for poor mental health was - 0.012 (95% CI: - 0.0144, - 0.0089), indicating slightly higher concentration of mental health problem among socioeconomically disadvantaged adults in Iran. Socioeconomic inequality in poor mental health was mainly explained by gender (19.93%) and age (12.70%). Region, SES itself, and physical activity were other important factors that contributed to the concentration of poor mental health among adults with low socioeconomic status. Conclusion There exists nearly equitable distribution in poor mental health among Iranian adults, but with important variations by gender, SES, and geography. These results suggested that interventional programs in Iran should focus on should focus more on socioeconomically disadvantaged people as a whole, with particular attention to the needs of women and those living in more socially disadvantaged regions. Keywords:Mental health; Socioeconomic inequality; Concentration index; Decompositio

High levels of γ-glutamyl hydrolase (GGH) are associated with poor prognosis and unfavorable clinical outcomes in invasive breast cancer

Background Previously, we performed analysis of gene expression in 46 axillary lymph node negative tumors and identified molecular gene signatures that resulted in different clinical outcomes. The aim of this study was to determine the correlation of γ-glutamyl hydrolase (GGH), fatty acid amide hydrolase (FAAH), Pirin (PIR) and TAF5-like RNA polymerase II, p300/CBP-associated factor (PCAF)-associated factor, 65 kDa (TAF5L), selected from identified gene signatures, with clinical outcomes as well as classical clinicopathological characteristics in primary invasive breast cancer patients. Methods The protein levels of GGH, FAAH, PIR and TAF5L were assessed by immunohistochemistry (IHC) on a panel of 80 primary invasive breast tumors. Quantitative real-time PCR (qRT-PCR) and western blot analysis were performed to verify the expression levels of the candidate biomarkers. Patient disease-specific survival (DSS) and recurrence-free survival (RFS) were evaluated using the Kaplan-Meier method. The prognostic biomarkers were identified by univariate analysis with a log-rank test and by multivariate analysis with Cox proportional hazards regression models. Results The GGH and FAAH protein levels were significantly up-regulated in invasive breast cancer tumors compared with adjacent non-cancerous tissues. Furthermore, the protein levels of GGH and FAAH were significantly correlated in tumor tissues. Tumoral GGH protein expression was significantly correlated with shorter DSS and RFS. Furthermore, the protein expression of GGH was positively correlated with undifferentiated tumors (BRE grade III) and ER/PR expressing tumors. Multivariate regression analysis showed that only GGH protein expression independently predicts DSS. No such correlations were found for FAAH, PIR and TAF5L protein expression. However, elevated protein levels of FAAH were positively associated with high number of lymph node involvement and upregulated levels of PIR were positively related with lymph node metastasis. The TAF5L was pronouncedly down-regulated in primary invasive breast cancer tissues compared to matched adjacent non-cancerous tissues. Conclusion These data show for the first time that cytoplasmic GGH might play a relevant role in the development and progression of invasive breast cancer, warranting further investigations. Our findings suggest that GGH serve as a potential biomarker of unfavorable clinical outcomes over short-term follow-up in breast cancer. The GGH may be a very attractive targeted therapy for selected patients

High levels of γ-glutamyl hydrolase (GGH) are associated with poor prognosis and unfavorable clinical outcomes in invasive breast cancer

Background Previously, we performed analysis of gene expression in 46 axillary lymph node negative tumors and identified molecular gene signatures that resulted in different clinical outcomes. The aim of this study was to determine the correlation of γ-glutamyl hydrolase (GGH), fatty acid amide hydrolase (FAAH), Pirin (PIR) and TAF5-like RNA polymerase II, p300/CBP-associated factor (PCAF)-associated factor, 65 kDa (TAF5L), selected from identified gene signatures, with clinical outcomes as well as classical clinicopathological characteristics in primary invasive breast cancer patients. Methods The protein levels of GGH, FAAH, PIR and TAF5L were assessed by immunohistochemistry (IHC) on a panel of 80 primary invasive breast tumors. Quantitative real-time PCR (qRT-PCR) and western blot analysis were performed to verify the expression levels of the candidate biomarkers. Patient disease-specific survival (DSS) and recurrence-free survival (RFS) were evaluated using the Kaplan-Meier method. The prognostic biomarkers were identified by univariate analysis with a log-rank test and by multivariate analysis with Cox proportional hazards regression models. Results The GGH and FAAH protein levels were significantly up-regulated in invasive breast cancer tumors compared with adjacent non-cancerous tissues. Furthermore, the protein levels of GGH and FAAH were significantly correlated in tumor tissues. Tumoral GGH protein expression was significantly correlated with shorter DSS and RFS. Furthermore, the protein expression of GGH was positively correlated with undifferentiated tumors (BRE grade III) and ER/PR expressing tumors. Multivariate regression analysis showed that only GGH protein expression independently predicts DSS. No such correlations were found for FAAH, PIR and TAF5L protein expression. However, elevated protein levels of FAAH were positively associated with high number of lymph node involvement and upregulated levels of PIR were positively related with lymph node metastasis. The TAF5L was pronouncedly down-regulated in primary invasive breast cancer tissues compared to matched adjacent non-cancerous tissues. Conclusion These data show for the first time that cytoplasmic GGH might play a relevant role in the development and progression of invasive breast cancer, warranting further investigations. Our findings suggest that GGH serve as a potential biomarker of unfavorable clinical outcomes over short-term follow-up in breast cancer. The GGH may be a very attractive targeted therapy for selected patients