Downregulated genes by silencing MYC pathway identified with RNA-SEQ analysis as potential prognostic biomarkers in gastric adenocarcinoma

通过 RNA-SEQ 分析确定沉默 MYC 通路下调的基因是胃腺癌的潜在预后生物标志物

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作者:Jersey Heitor da Silva Maués, Helem Ferreira Ribeiro, Raquel de Maria Maués Sacramento, Rafael Maia de Sousa, Raíssa Pereira de Tommaso, Bruno Dourado Kovacs Machado Costa, Paulo Cardoso Soares, Paulo Pimentel Assumpção, Caroline de Fátima Aquino Moreira-Nunes, Rommel Mário Rodriguez Burbano

Abstract

MYC overexpression is a common phenomenon in gastric carcinogenesis. In this study, we identified genes differentially expressed with a downregulated profile in gastric cancer (GC) cell lines with silenced MYC. The TTLL12, CDKN3, CDC16, PTPRA, MZT2B, UBE2T genes were validated using qRT-PCR, western blot and immunohistochemistry in tissues of 213 patients with diffuse and intestinal GC. We identified high levels of TTLL12, MZT2B, CDC16, UBE2T, associated with early and advanced stages, lymph nodes, distant metastases and risk factors such as H. pylori. Our results show that in the diffuse GC the overexpression of CDC16 and UBE2T indicate markers of poor prognosis higher than TTLL12. That is, patients with overexpression of these two genes live less than patients with overexpression of TTLL12. In the intestinal GC, patients who overexpressed CDC16 had a significantly lower survival rate than patients who overexpressed MZT2B and UBE2T, indicating in our data a worse prognostic value of CDC16 compared to the other two genes. PTPRA and CDKN3 proved to be important for assessing tumor progression in the early and advanced stages. In summary, in this study, we identified diagnostic and prognostic biomarkers of GC under the control of MYC, related to the cell cycle and the neoplastic process.

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