Analysis of Gene Expression in Early-Stage Ovarian Cancer

Abstract

Purpose: 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. Experimental Design: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. Results: 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 1tumors. 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). Conclusions: 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.

The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

“…We previously demonstrated that increased CD47 mRNA expression levels were correlated with poor clinical outcomes in patients with acute myeloid leukemia and non-Hodgkin's lymphoma (16,17). To determine if CD47 mRNA expression levels were also a prognostic factor in human solid tumors, we analyzed gene-expression data from several previously described cohorts of patients with ovarian cancers, gliomas, and glioblastomas (Table S1) (18)(19)(20)(21)(22)(23)(24)(25). In a univariate analysis, stratification of patients into "CD47 high" and "CD47 low" groups based on an optimum threshold revealed that high CD47 mRNA expression levels were associated with a decreased probability of progression-free ( Fig.…”

miRNA Landscape in Stage I Epithelial Ovarian Cancer Defines the Histotype Specificities

“…Data previously published by our group deciphered a molecular circuit in stage I EOC, revealing miR-200c as an independent prognostic factor (6,7). Focusing our study on the miRNA profiles, we studied the differences among stage I EOC histologic types looking for specific markers and regulatory circuits.…”

Protein expression patterns associated with advanced stage ovarian cancer

“…It has been suggested by several studies that different histological types of ovarian cancers represent distinct disease entities [4][5][6]; in fact, it appears that endometrioid ovarian cancer arises probably from the metaplastic Mullerian epithelium rather than the ovarian surface celomatic sheet, which is more likely in the case of serous carcinoma. This reflects the fact that gene expression profiles are different in the two histological types regardless of the stage and grade of the disease [7].…”