Abstract 549: Gene expression changes of GAEC1 in a large cohort of human cancer tissues

Abstract

Abstract Background: Gene amplified in esophageal cancer 1 (GAEC1) is a novel oncogene located at 7q22.1 and preliminary work on GAEC1 suggested that it has tumorigenic potential and over expression of GAEC1 is a critical step for carcinogenesis. However, because the initial work on this gene was undertaken in its oncogenic properties, there is currently a lack of information of the molecular roles of this novel gene in other cancers. This research is intended to investigate the expression pattern of GAEC1 mRNA in tissues and cell line models of cancer. Materials and methods: Approximately 856 human tissues and blood samples have been collected. This comprises 430 colorectal tissues 135 oesophageal tissues 254 thyroid tissues; 37 blood samples (25 oesophageal cancers and 12 healthy individuals). This study used nine cancer (oesophageal, colorectal and thyroid cancers) and two normal (oesophageal epithelial and colon epithelial cell line) cell lines. Histological samples (non-tumour, pre-cancerous and cancerous lesions) were collected and the pathology of these lesions were reviewed. The mRNAs of the selected samples were extracted by standard protocol. GAEC1 mRNA expression was studied by evaluating the quantitative amplification of GAEC1 RNA using quantitative real-time polymerase chain reaction. Results: GAEC1 mRNA expression levels were significantly altered in all selected cancer tissue models (colorectal, oesophageal and thyroid carcinomas). This level of GAEC1 was associated with tumour site, histological subtypes, and metastasis. At the mRNA level, 29% (n=61/210) of colorectal cancers, 22% (n=23/105)of oesophageal cancers and 7% (n=8/120) of thyroid cancers showed high GAEC1 expression (relative to control tissue). GAEC1 mRNA expression (mean) in oesophageal cancer blood samples showed 4 times higher expression compared to the control samples (p < 0.0001). Patients with high GAEC1 mRNA expression levels in their oesophageal cancer tissue had reduced survival period compared to patients with low GAEC1 mRNA levels (p=0.05). Conclusion: The current study noted multiple new findings, including relationships with clinical and pathological parameters with GAEC1 mRNA expression in three different types of cancers. The altered mRNA expression of GAEC1 and its correlation with different tissues samples and sites of tumour may also be important for the development of gene targeting therapies for cancers. Further research in unveiling GAEC1 protein structure and functional studies and post translational modifications will help in understanding the role of this oncogene in human carcinogenesis. Results of this study indicate that GAEC1 has an impact on human cancer pathogenesis. Citation Format: Vinod Gopalan, Robert A. Smith, Suja Pillai, Ali Salajegheh, Johnny Chuek-on Tang, Alfred KY Lam. Gene expression changes of GAEC1 in a large cohort of human cancer tissues. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 549. doi:10.1158/1538-7445.AM2014-549