Abstract 4201: Analysis of gene expression profile and signaling networks potentially involved in lymph node metastasis in esophageal squamous cell carcinoma
Authors: Sato-Kuwabara Yukie , Marchi Fabio Albuquerque , Klock Clóvis , Coimbra Felipe , Rogatto Silvia Regina , Soares Fernando Augusto 
Published: August 2012

Abstract
Esophageal squamous cell carcinoma (ESCC) is the 8th most common cancer worldwide and the 6th tumor in frequency in Brazil. Most of cases are diagnosed at an advanced stage and despite the improvement of various treatment modalities the overall survival rates still remain low. The aim of this study was to analyze the gene expression profile to identify the genes related to lymph node metastasis in ESCC samples. Genome-wide expression profiling was carried out in total RNA extracted from 17 frozen tissue samples using the Agilent Whole Human Genome Microarray 44K following the manufacturer's protocol. Data were extracted and flagged with Feature Extraction and processed using TMEV Software. A supervised hierarchical clustering was performed using the Pearson distance metric. Paired t-test analysis with 1000 permutations was performed to generate a list of differentially expressed genes from the comparison between the different groups. Only genes showing a false discovery rate (Q value) &lt;5% were accepted as differentially expressed. The Ingenuity Pathway Analysis (IPA) Software was used to assess the involvement of significantly differentially expressed genes in known pathways and networks. Hierarchical clustering showed two distinct groups according to lymph node metastasis: Group 1 comprised 6 node-negative cases and Group 2 with 11 node-positive cases. The gene expression profiling revealed 338 genes differentially expressed between the two groups, of which 321 showed lower expression and 17 showed a higher expression in cases of Group 2 when compared to those of Group 1. According to IPA analysis five significant networks could be defined comprising the genes differentially expressed between the two groups. The first network with a score of 43 comprised 21 of the differentially expressed genes and was associated to functions as cell-to-cell signaling and interaction, lipid metabolism and molecular transport. The second network (score 22, 13 genes) was related to nucleic acid metabolism, small molecules biochemistry and energy production. The third network (score 21, 14 genes) was associated to cellular signaling, molecular transport and small molecular biochemistry. The network 4 (score of 21, 12 genes) was associated to cancer, DNA replication, recombination and repair and gene expression. The fifth network (score 21, 12 genes) was related to cellular movement, cardiovascular system development and function and neurological disease. In this study, it was detected genes differentially expressed between cases with and without lymph node metastasis involved in important signaling networks that could have an impact on tumor development or progression in ESCC. The identified genes might be useful as a first step to identify molecular markers to predict lymph node metastasis for improved diagnostic and therapeutic modalities in this tumor.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4201. doi:1538-7445.AM2012-4201