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GENE EXPRESSION PROFILE OF ESOPHAGOGASTRIC JUNCTION ADENOCARCINOMA DIFFERS FROM DISTAL GASTRIC ADENOCARCINOMA
Sergio B. Marques
*, Tatiane K. Furuya, Alexis G. Carrasco, Marina A. Pereira, Marcus F. Ramos, Miyuki V. Uno, Maria J. Ferreira Alves, Diogo Araujo, Roger J. Chammas, Fauze Maluf-Filho, Ulysses Ribeiro, Adriana V. Safatle-Ribeiro
Gastroenterology, University of Sao Paulo, Sao Paulo, SP, Brazil
BACKGROUND: Esophagogastric junction adenocarcinoma (EGJA) incidence has been increasing worldwide. While EGJA tumors are associated with gastroesophageal reflux and obesity, distal gastric tumors are commonly related to
Helicobacter pylori infection and chronic atrophic gastritis. Distinct risk factors may reflect differences in the expression of genes involved in inflammation, immune response, and metabolism. Accumulation of molecular alterations may have an impact on prognosis.
AIM: To compare the gene expression profile of distal gastric (G = combined body and antrum) tumors with each topographic location of EGJA according to Siewert classification (SW I, SW II, and SW III).
METHODS: A total of 85 patients were included from a retrospective cohort. Gene expression analysis was conducted using a high-throughput nanofluidic qRT-PCR platform (Biomark HD System, Fluidigm), targeting 68 genes related to malignancy/metastasis, multiple growth signaling pathways, immune response, and tumor suppressor genes. Comparative analysis of G tumors (n=40) with each Siewert classification (SW I, n=15; SW II, n=17; SW III, n=13) was performed. Genes were selected based on significant differences (Fold Change > 1.5 and p-value < 0.05) observed exclusively in one of the comparisons: SW I vs. G, SW II vs. G, or SW III vs. G.
RESULTS: The mean age was 65.3 years, and 59% were male. Ten genes were differentially expressed between SW I and G group, with nine of them overexpressed: ANGPTL4, CDH1, CEACAM6, HMOX2, IL18, MYC, NF2L2, TGFB1, WNT5A, and one downregulated (CD40). Genes overexpressed in SW I patients were associated with angiogenesis (ANGPTL4, MYC), tumor progression (ANGPTL4, CEACAM6, HMOX2, IL18, TGFB1), resistance to oxidative stress (NF2LE, HMOX2), and resistance to apoptosis (MYC, CEACAM6). Compared to G group, only PARP1 gene was overexpressed in SW II, while CCND1 and HIF1A genes were overexpressed in SW III (Figure 1). Among EGJA, SW I had the worst prognosis.
CONCLUSION: EGJA gene expression profile demonstrates a distinct tumor biology compared to G tumors. These findings may be used to better understand the tumor carcinogenesis and progression, as well as for treatment management.
Figure 1. Gene expression of esophagogastric junction compared to gastric (body and antrum) adenocarcinomas
Figure 2. Overall survival according to tumor location
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