Abstract 3155: Integrated analysis of genomic and transcriptomic data in esophageal squamous cell carcinoma.
Authors: Sato-Kuwabara Yukie , Marchi Fabio Albuquerque , Klock Clóvis , Scapulatempo Cristovam , Coimbra Felipe , Rogatto Silvia Regina , Soares Fernando Augusto 
Published: August 2014

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. In order to identify new possible molecular markers, genomic and transcriptomic data were evaluated using integrative analysis in ESCC samples. Thirty frozen samples of ESCC were carried out in genome-wide expression (GWE) profiling using the Agilent Whole Human Genome Microarray 44K and in Array-CGH (aCGH) using the Agilent Human Genome CGH Microarray 44K following the manufacturer's protocol. Data were extracted and flagged with Feature Extraction and processed using NEXUS 6.0 and TMEV 4.8 Software. A subset of genes identified by the integrated analysis was analyzed for signaling networks using Ingenuity Pathway Analysis (IPA) software. The aCGH analysis revealed 14 significant genomic alterations including 7 gains and 7 losses. Gains were detected at 3q27.3-q28, 3q28-q29, 3q29, 7q21.3-q22.1, 8p11.23-p11.2, 11q13.2-q13.4 and 12p13.31; losses were found at 1p21.1-p13.3, 3p11.1-q11.1, 3p12.1-p11.2, 6q16.3, 9q21.13, 9p21.3 and 13q21.31. A total of 375 genes were mapped to these regions of which 343 genes were involved in genomic gains and 32 in losses. GWE profile identified 1770 differentially expressed genes in comparison with normal tissue including 573 up regulated and 1197 down-regulated. The integrated analysis showed that genomic and transcriptomic results were concordant in 39 genes, in which 36 were up regulated and involved in gain of DNA copy number and 3 genes were down-regulated and associated to genomic losses. According to IPA analysis three significant networks could be defined comprising these genes. The first network comprised 14 of the concordant genes and was associated to functions as cellular assembly and organization, cardiovascular system development and function and cell morphology. The second network (11 genes) was related to cancer, immunological disease and cell cycle. The third network (9 genes) was associated to cancer, RNA post-transcriptional modification and organismal development. A total of 11 genes were involved in genomic gains by aCGH but were considered down-regulated by GWE profiling, while two genes were involved in losses but their transcripts were up-regulated. The IPA analysis showed that these genes are associated to function as drug metabolism, small molecule biochemistry and nucleic acid metabolism. In this study, it was detected significant genomic alterations and genes differentially expressed involved in important signaling networks that could have an impact on tumor development or progression in ESCC. These genes might be useful as a first step to identify molecular markers for improved diagnostic and therapeutic modalities in this tumor.
Citation Format: Yukie Sato-Kuwabara, Fabio Albuquerque Marchi, Clóvis Klock, Cristovam Scapulatempo, Felipe Coimbra, Silvia Regina Rogatto, Fernando Augusto Soares. Integrated analysis of genomic and transcriptomic data in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3155. doi:10.1158/1538-7445.AM2013-3155