Abstract

BackgroundEndometrial cancer is the most common gynecologic malignancy in developed countries and little is known about the underlying mechanism of stage and disease outcomes. The goal of this study was to identify differentially expressed genes (DEG) between late vs. early stage endometrioid adenocarcinoma (EAC) and uterine serous carcinoma (USC), as well as between disease outcomes in each of the two histological subtypes.Methodology/Principal FindingGene expression profiles of 20 cancer samples were analyzed (EAC = 10, USC = 10) using the human genome wide illumina bead microarrays. There was little overlap in the DEG sets between late vs. early stages in EAC and USC, and there was an insignificant overlap in DEG sets between good and poor prognosis in EAC and USC. Remarkably, there was no overlap between the stage-derived DEGs and the prognosis-derived DEGs for each of the two histological subtypes. Further functional annotation of differentially expressed genes showed that the composition of enriched function terms were different among different DEG sets. Gene expression differences for selected genes of various stages and outcomes were confirmed by qRT-PCR with a high validation rate.ConclusionThis data, although preliminary, suggests that there might be involvement of distinct groups of genes in tumor progression (late vs. early stage) in each of the EAC and USC. It also suggests that these genes are different from those involved in tumor outcome (good vs. poor prognosis). These involved genes, once clinically verified, may be important for predicting tumor progression and tumor outcome.

Highlights

  • Endometrial cancer is the most common gynecologic malignancy in developed countries, including an estimated 42,160 new cases in the United States in 2009 and claiming almost 7,780 lives [1]

  • We identified 274 differentially expressed genes (DEG) at significance level (p,0.01) in patients with uterine serous carcinoma (USC), with 165 genes up-regulated and 109 genes down-regulated in late stage disease

  • For stage comparison in patients with endometrioid adenocarcinoma (EAC), we identified 111 significant DEGs (p,0.01), with 92 genes up-regulated and 19 genes were down-regulated in late stages

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Summary

Introduction

Endometrial cancer is the most common gynecologic malignancy in developed countries, including an estimated 42,160 new cases in the United States in 2009 and claiming almost 7,780 lives [1]. EACs are the most frequent subtype and account for more than 80% of all endometrial adenocarcinomas They are associated with obesity, exogenous hormonal therapy and they tend to present as low grade, early stage tumors with good outcomes, often cured with surgery alone. While USCs represent a minority of total endometrial cancer cases they are responsible for a disproportionate number of deaths [3,4] They are high grade tumors with deep myometrial invasion and lymphovascular involvement [5]. The goal of this study was to identify differentially expressed genes (DEG) between late vs early stage endometrioid adenocarcinoma (EAC) and uterine serous carcinoma (USC), as well as between disease outcomes in each of the two histological subtypes

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