Gene expression profiling of human ovarian tumours

• Published in: British journal of cancer Vol. 95; no. 8; pp. 1092 - 1100
• Main Authors: BIADE, S, MARINUCCI, M, SCHICK, J, ROBERTS, D, WORKMAN, G, SAGE, E. H, O'DWYER, P. J, LIVOLSI, V. A, JOHNSON, S. W
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 23.10.2006
• Subjects: Adenocarcinoma, Clear Cell - genetics; Adenocarcinoma, Clear Cell - metabolism; Adenocarcinoma, Clear Cell - pathology; Biological and medical sciences; Calcium-Binding Proteins - analysis; Calcium-Binding Proteins - genetics; Cancer research; CD24 Antigen - analysis; CD24 Antigen - genetics; Cluster Analysis; Cystadenocarcinoma, Mucinous - genetics; Cystadenocarcinoma, Mucinous - metabolism; Cystadenocarcinoma, Mucinous - pathology; Cystadenocarcinoma, Serous - genetics; Cystadenocarcinoma, Serous - metabolism; Cystadenocarcinoma, Serous - pathology; Extracellular Matrix Proteins - analysis; Extracellular Matrix Proteins - genetics; Female; Female genital diseases; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - genetics; Genetics and Genomics; Genomics; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Medical prognosis; Medical research; Medical sciences; Oligonucleotide Array Sequence Analysis - methods; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Tumors; Womens health; United States > US; Human; ovarian cancer; Ovary cancer; borderline tumors; expression profiling; DNA chip; Malignant tumor; Female genital diseases; Gene expression profile; Ovarian diseases; microarray; Cancerology; Borderline tumor; Ovarian tumor
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6603346

There is currently a lack of reliable diagnostic and prognostic markers for ovarian cancer. We established gene expression profiles for 120 human ovarian tumours to identify determinants of histologic subtype, grade and degree of malignancy. Unsupervised cluster analysis of the most variable set of expression data resulted in three major tumour groups. One consisted predominantly of benign tumours, one contained mostly malignant tumours, and one was comprised of a mixture of borderline and malignant tumours. Using two supervised approaches, we identified a set of genes that distinguished the benign, borderline and malignant phenotypes. These algorithms were unable to establish profiles for histologic subtype or grade. To validate these findings, the expression of 21 candidate genes selected from these analyses was measured by quantitative RT-PCR using an independent set of tumour samples. Hierarchical clustering of these data resulted in two major groups, one benign and one malignant, with the borderline tumours interspersed between the two groups. These results indicate that borderline ovarian tumours may be classified as either benign or malignant, and that this classifier could be useful for predicting the clinical course of borderline tumours. Immunohistochemical analysis also demonstrated increased expression of CD24 antigen in malignant versus benign tumour tissue. The data that we have generated will contribute to a growing body of expression data that more accurately define the biologic and clinical characteristics of ovarian cancers.