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Research Paper|Volume 12, Issue 24|pp 24651—24670

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

Jersey Heitor da Silva Maués1,2, Helem Ferreira Ribeiro1,3, Raquel de Maria Maués Sacramento2, Rafael Maia de Sousa2, Raíssa Pereira de Tommaso2, Bruno Dourado Kovacs Machado Costa2, Paulo Cardoso Soares2, Paulo Pimentel Assumpção4, Caroline de Fátima Aquino Moreira-Nunes5, Rommel Mário Rodriguez Burbano1,2
  • 1Laboratory of Human Cytogenetics, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil
  • 2Laboratory of Molecular Biology, Ophir Loyola Hospital, Belém, Belém 66063-240, PA, Brazil
  • 3Center of Biological and Health Sciences, Department of Biomedicine, University of Amazon, Belém 66060-000, PA, Brazil
  • 4Oncology Research Nucleus, University Hospital João de Barros Barreto, Federal University of Pará, Belém 66073-000, PA, Brazil
  • 5Laboratory of Pharmacogenetics, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza 60430-275, CE, Brazil
* Equal contribution
Received: June 27, 2020Accepted: October 31, 2020Published: December 22, 2020
https://doi.org/10.18632/aging.202260

Copyright: © 2020 Heitor da Silva Maués et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.