Gene Expression Profiling and Cancer-Related Pathways in Type I Endometrial Carcinoma

Introduction: Malignant transformation of type I endometrium involves alteration in gene expression with subsequent uncontrolled proliferation of altered cells. Objective: The main objective of the present study was to identify the cancer-related genes and gene pathways in the endometrium of healthy and cancer patients. Materials and Methods: Thirty endometrial tissues from healthy and type I EC patients were subjected to total RNA isolation. The RNA samples with good integrity number were hybridized to a new version of Affymetrix Human Genome GeneChip 1.0 ST array. We analyzed the results using the GeneSpring 9.0 GX and the Pathway Studio 6.1 software. For validation assay, quantitative real-time polymerase chain reaction was used to analyze 4 selected genes in normal and EC tissue. Results: Of the 28,869 genes profiled, we identified 621 differentially expressed genes (2-fold) in the normal tissue and the tumor. Among these genes, 146 were up-regulated and 476 were down-regulated in the tumor as compared with the normal tissue ( P < 0.001). Up-regulated genes included the v-erb-a erythroblastic leukemia viral oncogene homolog 3 ( ErbB3 ), ErbB4 , E74-like factor 3 ( ELF3 ), and chemokine ligand 17 ( CXCL17 ). The down-regulated genes included signal transducer and activator transcription 5B ( STAT5b ), transforming growth factor β receptor III ( TGFβ3 ), caveolin 1 ( CAV1 ), and protein kinase C alpha ( PKCA ). The gene set enrichment analysis showed 10 significant gene sets with related genes ( P < 0.05). The quantitative polymerase chain reaction of 4 selected genes using similar RNA confirmed the microarray results ( P < 0.05). Conclusions: Identification of molecular pathways with their genes related to type I EC contribute to the understanding of pathophysiology of this cancer, probably leading to identifying potential biomarkers of the cancer.