Gene Expression Meta-Analysis Identifies Chromosomal Regions Involved in Ovarian Cancer Survival

Ovarian cancer cells exhibit complex karyotypic alterations causing deregulation of numerous genes. Some of these genes are probably causal for cancer formation and local growth, whereas others are causal for metastasis and recurrence. By using publicly available data sets, we have investigated the relation of gene expression and chromosomal position to identify chromosomal regions of importance for early recurrence of ovarian cancer. By use of "Gene Set Enrichment Analysis," we have ranked chromosomal regions according to their association to survival. Over-representation analysis including 1-4 consecutive cytogenetic bands identified regions with increased expression for chromosome 5q12-14, and a very large region of chromosome 7 with the strongest signal at 7p15-13 among tumors from short-living patients. Reduced gene expression was identified at 4q26-32, 6p12-q15, 9p21-q32, and 11p14-11. We summarized mutation load in these regions by a combined mutation score that is statistical significantly associated to survival by analysis in the data sets used for identification of the regions. Furthermore, the prognostic value of the combined mutation score was validated in an independent large data set using death (P = 0.015) and recurrence (P = 0.002) as outcome. The combined mutation score is strongly associated to upregulation of several growth factor pathways. (C) 2009 Wiley-Liss, Inc.