Changes in tumorigenesis- and angiogenesis-related gene transcript abundance profiles in ovarian cancer detected by tailored high density cDNA arrays

Background: Complementary DNA array analysis of gene expression has a poten tial application for clinical diagnosis of disease processes. However, acce ssibility, affordability, reproducibility of results, and management of the data generated remain issues of concern. Use of cDNA arrays tailored for s tudies of specific pathways, tissues, or disease states may render a cost- and time-effective method to define potential hallmark genotype alterations . Materials and Methods: We produced a 332-membered human cDNA array on nylon membranes tailored for studies of angiogenesis and tumorigenesis in reprod uctive disease. We tested the system for reproducibility using a novel stat istical approach for analysis of array data and employed the arrays to inve stigate gene expression alterations in ovarian cancer. Results: Intra-assay analysis and removal of agreement outliers was shown t o be a critical step prior to interpretation of cDNA array data. The system revealed highly reproducible results, with intermembrane coefficient of re producibility of +/-0.98. Comparison of placental and ovarian sample data c onfirmed expected differences in angiogenic profiles and tissue-specific ma rkers, such as human placental lactogen (hPL). Analysis of expression profi les of five normal ovary and four poorly differentiated serous papillary ov arian adenocarcinoma samples revealed an overall increase in angiogenesis-r elated markers, including vascular endothelial growth factor (VEGF) and ang iopoietin-1 in the diseased tissue. These were accompanied by increases in immune response mediators (e.g. HLADR, Ron), apoptotic and neoplastic marke rs (e.g. BAD protein, b-myb), and novel potential markers of ovarian cancer , such as cofilin, moesin, and neuron-restrictive silencer factor (REST) pr otein. Conclusions: In-house production of tailored cDNA arrays, coupled to compre hensive analysis of resulting hybridization profiles, provides an accessibl e, reliable, and highly effective method of applying array technology to st udy disease processes. In the ovary, abundance of specific tumor markers, i ncreased macrophage recruitment mediators, a late-stage angiogenesis profil e, and the presence of chemoresistance-related markers distinguished normal and advanced ovarian cancer tissue samples. Detection of such parallel cha nges in pathway- and tissue-specific markers may prove a hallmark ready for application in reproductive disease diagnostic and therapeutic development s.