Differentially Expressed Genes in Early Stages Uterine Serous Carcinomas in Comparison to G3 and G1 Endometrioid Adenocarcinoma.
Susanna Syriac, Dan Wang, Joshua Kesterson, Kunle Odunsi, Shashikant Lele, Song Liu, Paulette Mhawech-Fauceglia. Roswell Park Cancer Institute, Buffalo, NY
Background: Clinical studies demonstrated that early stages uterine serous carcinoma (USC) had almost similar outcome in comparison to early stages high grade endometrioid adenocarcinoma (EAC)-G3. The aim of this study is to explore the genetic fingerprints of these tumors that may explain their similar outcome.
Design: A transcriptome analysis was performed using the human genome wide illumina bead microarrays carrying 48,000 genes to profile stage I USC (n=11) vs. stage I EAC-G3 (n=11) and vs. stage I EAC-G1 (n=11), respectively. The expressions of 15 genes were selected for validation and determined using Taqman RT-PCR gene expression.
Results: We identified 988 differentially expressed genes (DEGs) between USC and EAC-G3 with 522 genes specific to USC and 1,499 DEGs between USC vs. EAC-G1 with 1,063 genes specific to USC. The up-regulated genes specific to USC were genes involved in cell proliferation, invasion and metastasis (SNCG), cell adhesion (MSN), tumor progression (LMNA), cell cycle (TBX2) and tumor development, growth and angiogenesis (IRS2). The down regulated genes were involved in suppressing tumor metastasis (NME5), reduce cell growth (ALCAM), tumor suppressor (CEACAM1), and slow cancer progression (TFF3). Although, many of these genes were novel genes to USC, they were found in other cancer types such as liver, colon, breast and lung cancers. Over-regulation of some genes had been proven to predict poor prognosis such as SNCG and IRS2 in colon cancer, and downregulation of NME5 to be a predictor of metastatic potential in breast cancer. In addition, genes like ALCAM and SNCG were implicated to be associated with chemoresistance in pancreatic and uterine cancer.
Conclusions: We found that stage I USC has relatively similar gene fingerprints in comparison to EAC-G3 than to EAC-G1. Numerous novel DEGs and their transcripts found to be specific to USC might have potential prognostic and therapeutic impact on patients with uterine cancer. However, our results should be confirmed by larger studies to evaluate the usefulness of some genes as biomarkers in endometrial cancer. Nevertheless, we believe that our findings shed meaningful insights into the clinical study of endometrial cancer patients that warrant further investigation.
Category: Gynecologic & Obstetrics
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 167, Wednesday Afternoon