Abstract C05: Analysis of oxidative modified proteins in serous subtype of ovarian carcinoma

Abstract

Abstract Serous subtype of ovarian cancer accounts for approximately 60% to 80% of ovarian cancer cases and is by far the most aggressive histology. Fewer than 25% of the serous ovarian cancer cases are detected at an early stage (stages I and II), a statistic which reflects grimly on the low survival rates, especially among African-American women. Elevated levels of reactive oxygen species (ROS) are one of many of known and suspected risk factors associated with ovarian cancer. Oxidative stress, which results from an imbalance between ROS and antioxidant capacities, can cause a wide range of direct or indirect DNA damage. There are extensive DNA repair systems that can correct DNA damage caused by ROS before cell replication and mutation fixation. Given that serous cancer subtype is considered to have originated from the fallopian epithelium mucosa that was exposed to immense physiological changes, driven by cyclically altering hormone levels as a result of ovulation. The influence of ovulation is a cause of increased oxidative stress. In this study, we applied spectrophotometric DNPH assay, two dimension gel electrophoresis (2-D SDS-PAGE), and Oxidized protein western blot analysis to identify and evaluate the level of oxidative modified protein, using derivatisation of protein carbonyl group with 2,4-dinitrophenylhyrdozine(DNPH) assay in the obtained 155 snap-freeze primary serous epithelial ovarian tissues including, normal, normal surrounding, cystoadenoma, borderline and carcinoma with age range of 65±12, (55% Caucasian 45% Africa American). Our results showed that the index of carbonyl protein /total protein increased by onset and progression of the serous ovarian malignancy. The elevation of oxidized protein among African American was 40 % higher than Caucasian in advanced stages of disease. SDS-PAGE profiles and western blot analysis of oxidized proteins showed a distinct protein pattern among cancerous and non-cancerous tissues. Our study suggests that level of oxidative stress, may involve the selective modification of some enzymes and structural proteins and play a role in etiological differences that may exist between stages of benign and invasive epithelial ovarian tumors. This study was funded in part as a result of the grants from NIH-CHDRD CA150317 and NCI CA150039. Citation Format: Sharifeh Mehrabi, Shakeria Cohen, Edward E. Partridge, Felix O. Aikhionbare. Analysis of oxidative modified proteins in serous subtype of ovarian carcinoma. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C05. doi:10.1158/1538-7755.DISP13-C05