Abstract
Gastric cancer (GC) is the fourth most common cancer in the world. In Brazil it is the fourth common in males and the sixth in females, and in 2016 12,920 new cases for men and 7,600 for women were expected. GC is a multifactorial disease comprehending lifestyle, aging, genetic, socioeconomic factors, and also infection by Helicobacter pylori, which has been attributed in 80% of the cases and Epstein-Barr virus (present in 6-10% of cases). One of the great problems of gastric cancer is the late disease detection caused by the nonspecific symptomatology in early stages which is associated with poor prognosis. According to Lauren classification the adenocarcinoma presents in two types: intestinal (well differentiated with cohesive neoplastic cells, forming gland-like tubular strictures) and diffuse (poorly differentiated with infiltration and thickening of the stomach wall without the formation of a discrete mass). Innovative technologies have been used in the last years to identify alterations in gastric cancer cell biology, e.g., several genetic abnormalities such as aberrant genes, copy number variation, microRNAs, and long noncoding RNAs were identified as possible biomarkers in these studies. However, the molecular mechanisms leading to gastric cancer and those responsible for its progression are not clearly understood; moreover, almost all studies' data were described from Asias or Central America populations. Thus, much of the information in the literature cannot be considered general for all populations. For this, the aim of this work was to analyze by microarrays the profile of Brazilian intestinal gastric cancer patients in relation to other populations. To address this hypothesis, we used chip arrays to evaluate the gene expression profiles from Brazilian intestinal gastric cancer patients compared to samples from normal mucosa of the same patients. RNA samples were obtained using RNeasy Mini kit (Qiagen, CA, USA). RNAs were prepared and hybridized to GeneChip Human Gene 1.0 ST Arrays (Affymetrix, CA, USA). The data were analyzed using Partek® with differentially expressed genes with a ≥5-fold change used as criteria to define overexpression or downregulation. ChipArray assay with Brazilian patients samples revealed 57 differentially expressed between tumor and nontumor tissues. To confirm the obtained chip array results, quantitative PCR (RT-qPCR) of some overexpressed genes such MMP7, SPARC, and TIMP1 and downregulated genes such as CHGA, KRT20, GIF, AKR1C2, and PGA4 was performed. Moreover, an unsupervised analysis with microarrays from different studies in worldwide using this Brazilian molecular signature was executed. For this purpose, cell intensity (CEL) files from populations with intestinal gastric cancer worldwide, storing probe-level intensity data were downloaded from NCBI's Gene Expression Omnibus (GEO) and the simpleAffy Bioconductor R package was used to preprocess all raw data files. The MetaCoreTM software (GeneGO Inc., Encinitas, CA) was used to access the processes and pathways associated with the data. The results revealed that 38 genes from Brazilian intestinal gastric cancer molecular signature could successfully classify intestinal gastric tumor from nontumor in worldwide patients. In silico analyses of these genes showed that important biologic process were altered in cancer tissues, e.g., extracellular matrix remodeling and differentiation of gastric mucosa. Altogether the results showed that a molecular signature exists for all intestinal gastric cancer compared to nontumor counterpart regardless of the population, and this molecular signature is inserted into processes important in cell homeostasis. This new gene panel may help guide investigation of new targets in development of new therapy agents more specific in treatment of patients with intestinal gastric cancer.
Citation Format: Everton Cruz Santos, Renata Binato, Demachki Samia, Paulo Pimentel Assumpção, Eliana Abdelhay. Brazilian intestinal gastric cancer displays a common molecular signature with worldwild [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A85.
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