Expression profile of genes associated with the histaminergic system estimated by oligonucleotide microarray analysis HG-U133A in women with endometrial adenocarcinoma

Abstract

Introduction: Influence of histamine on tumor development remains obscure. The exact mechanism of this action is not known. Different data indicate high concentrations of histamine in tumor tissues, such as malignant melanoma, breast cancer, colon carcinoma, lymphomas and leukemia. To the best of our knowledge, the literature offers no reports about the role of histamine and of differences between expression patterns of histamine-related genes in endometrial cancer. Aim: The aim of the study was a comparative analysis of the gene expression profile involved with histaminergic system in endometrioid endometrial cancer in relation to histologically normal endometrium, and identification of differentiation genes whose transcriptional activity significantly differs in pathomorphological grades G1,G2, G3 of endometrial cancer as compared to the control group. Material and methods: Total RNA was extracted from 24 endometrial probes using TRIzol reagent (Invitrogen). The expression profile of 119 transcripts associated with histaminergic system was assessed using oligonucleotide microarrays of HG-U133A (Affymetrix). After normalization of the results with RMA Express software, differentiation genes were mined by the use of one-way analysis ANOVA and U Mann-Whitney test carried out in Gene Spring 11.5 software. Results: Among 119 transcripts, 14 expressed more than 1.5-fold change and were significant at p<0.05 in endometrioid endometrial cancer in relation to the normal endometrium. Further analysis led to the identification of differentially expressed genes in grades G1, G2 and G3 of endometrial adenocarcinoma as compared to the control group, which were specific for each of the studied groups in grade G1 (CPA3), in grade G2 (HNMT, LYN, DPT, ITPKB, RASA4, APP, RAB11FIP1, YWHAZ, VAMP8, RAB25) and in grade G3 (HRH3). Conclusions: Our results confirmed the role of the histaminergic system in the pathogenesis of endometrial adenocarcinoma. The observed differences in the expression of those genes, depending on the grade of adenocarcinoma, may indicate an important role of the isolated differentiation genes in endometrial tumorigenesis.