title: New potential ligand-receptor signaling loops in ovarian cancer identified in multiple gene expression studies.
abstract: Based on the hypothesis that gene products involved in the same biological process would be coupled at transcriptional level, a previous study analyzed the correlation of the gene expression patterns of ligand-receptor (L-R) pairs to discover potential autocrine/paracrine signaling loops in different cancers (Graeber and Eisenberg. Nat Genet 2001; 29:295). By refining the starting database, a list of 511 L-R pairs was compiled, combined to eight data sets from a single pathology, epithelial ovarian cancer, and examined as a proof-of-principle of the statistical and biological validity of the correlation of the L-R gene expression patterns in cancer. Analysis revealed a Bonferroni-corrected significant correlation of 105 L-R pairs in at least one data set and, by systematic analysis, identified 39 more frequently correlated L-R pairs, 7 of which were already biologically confirmed. In four data sets examined for an L-R correlation associated with patient survival time, 15 L-R pairs were significantly correlated in short surviving patients in two of the data sets. Immunohistochemical analysis of one of the newly identified correlated L-R pairs (i.e., EFNB3-EPHB4) revealed the correlated expression of ephrin-B3 and EphB4 proteins in 45 of 55 epithelial ovarian tumor samples (P < 0.0001). Together, these data not only support the validity of cross-comparison analysis of gene expression data because known and expected correlations were confirmed but also point to the promise of such analysis in identifying new L-R signaling loops in cancer.
authors.affiliation: Unit of Molecular Therapies, Department of Experimental Oncology, Istituto Nazionale Tumori FIRC di Oncologia Molecolare, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Castellano
authors.forename: James F
authors.initials: JF
authors.lastname: Reid
authors.forename: Paola
authors.initials: P
authors.lastname: Alberti
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Carcangiu
authors.forename: Antonella
authors.initials: A
authors.lastname: Tomassetti
authors.forename: Silvana
authors.initials: S
authors.lastname: Canevari
mesh_terms: D036389:Ephrin-B3 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism*; D036224:Receptor, EphB4 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D036389:Ephrin-B3; D008024:Ligands; D011956:Receptors, Cell Surface; D036224:Receptor, EphB4