Background:The purpose of this study was to identify genes that are differentially expressed in chemosensitive serous papillary ovarian carcinomas relative to those expressed in chemoresistant tumours.Methods:To identify novel candidate biomarkers, differences in gene expression were analysed in 26 stage IIIC/IV serous ovarian adenocarcinomas (12 chemosensitive tumours and 14 chemoresistant tumours). We subsequently investigated the immunohistochemical expression of GRIA2 in 48 independent sets of advanced ovarian serous carcinomas.Results:Microarray analysis revealed a total of 57 genes that were differentially expressed in chemoresistant and chemosensitive tumours. Of the 57 genes, 39 genes were upregulated and 18 genes were downregulated in chemosensitive tumours. Five differentially expressed genes (CD36, LIFR, CHL1, GRIA2, and FCGBP) were validated by quantitative real-time PCR. The expression of GRIA2 was validated at the protein level by immunohistochemistry, and patients with GRIA2 expression showed a longer progression-free and overall survival (P=0.051 and P=0.031 respectively).Conclusions:We found 57 differentially expressed genes to distinguish between chemosensitive and chemoresistant tumours. We also demonstrated that the expression of GRIA2 among the differentially expressed genes provides better prognosis of patients with advanced serous papillary ovarian adenocarcinoma.
Background: Within the US Department of Veterans Affairs (VA), breast cancer prevalence has more than tripled from 1995 to 2012. Women veterans may be at an increased breast cancer risk based on service-related exposures and posttraumatic stress disorder (PTSD). Methods: Women veterans aged ≥ 35 years with no personal history of breast cancer were enrolled at 2 urban VA medical centers. We surveyed women veterans for 5-year and lifetime risks of invasive breast cancer using the Gail Breast Cancer Risk Assessment Tool (BCRAT). Data regarding demographics, PTSD status, eligibility for chemoprevention, and genetic counseling were also collected. Descriptive statistics were used to determine results. Results: A total of 99 women veterans participated, of which 60% were Black. In total, 35% were high risk with a 5-year BCRAT > 1.66%. Breast biopsies had been performed in 22% of our entire population; 57% had a family history positive for breast cancer. Comparatively, in our high-risk Black population, 33% had breast biopsies and 94% had a family history. High-risk patients were referred for chemoprevention; 5 accepted and 13 were referred for genetic counseling. PTSD was present in 31% of the high-risk subgroup. Conclusions: A high percentage of Black patients participated in this pilot study, which also showed an above average rate of PTSD among women veterans who are at high risk for developing breast cancer. Historically, breast cancer rates among Black women are lower than those found in the general population. High participation among Black women veterans in this pilot study uncovered the potential for further study of this population, which is otherwise underrepresented in research. Limitations included a small sample size, exclusively urban population, and self-selection for screening. Future directions include the evaluation of genetic and molecular mutations in high risk Black women veterans, possibly even a role for PTSD epigenetic changes.
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