Abstract
Gene expression profile was analyzed in 68 stage I and 15 borderline ovarian cancers to determine if different clinical features of stage I ovarian cancer such as histotype, grade, and survival are related to differential gene expression. Tumors were obtained directly at surgery and immediately frozen in liquid nitrogen until analysis. Glass arrays containing 16,000 genes were used in a dual-color assay labeling protocol. Unsupervised analysis identified eight major patient partitions, one of which was statistically associated to overall survival, grading, and histotype and another with grading and histotype. Supervised analysis allowed detection of gene profiles clearly associated to histotype or to degree of differentiation. No difference was found between borderline and grade 1 tumors. As to recurrence, a subset of genes able to differentiate relapsers from nonrelapsers was identified. Among these, cyclin E and minichromosome maintenance protein 5 were found particularly relevant, as their expression was inversely correlated to progression-free survival (P = 0.00033 and 0.017, respectively). Specific molecular signatures define different histotypes and prognosis of stage I ovarian cancer. Mucinous and clear cells histotypes can be distinguished from the others regardless of tumor grade. Cyclin E and minichromosome maintenance protein 5, whose expression was found previously to be related to a bad prognosis of advanced ovarian cancer, appear to be potential prognostic markers in stage I ovarian cancer too, independent of other pathologic and clinical variables.
Highlights
Gene expression profile was analyzed in 68 stage I and 15 borderline ovarian cancers to determine if different clinical features of stage I ovarian cancer such as histotype, grade, and survival are related to differential gene expression
Many groups have applied cDNA microarray technology to the study of advanced epithelial ovarian cancer (EOC) or cell lines derived from EOC (14 – 18), but very little is known about stage I and borderline carcinomas, which, relatively rare, are potentially more
Cyclin E and minichromosome maintenance protein 5 (MCM5) were found up-regulated in relapsing patients before chemotherapy and their expression levels correlated with overall survival and progression-free survival.This study suggests the potential use of cyclin E and MCM5 as predictive biomarkers for relapse in stage I EOC
Summary
Gene expression profile was analyzed in 68 stage I and 15 borderline ovarian cancers to determine if different clinical features of stage I ovarian cancer such as histotype, grade, and survival are related to differential gene expression. In spite of much recent preclinical and clinical efforts to identify novel markers and investigate new therapies, epithelial ovarian cancer (EOC) remains the fourth most common cause of cancer-related death in women in the western world, with f70% of patients dying within 5 years of diagnosis (1 – 4). This high death rate results from late diagnosis, when the disease has spread beyond the pelvis (stage III and IV). Many groups have applied cDNA microarray technology to the study of advanced EOC or cell lines derived from EOC (14 – 18), but very little is known about stage I and borderline carcinomas, which, relatively rare, are potentially more
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