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

Aging (Albany NY). 2020 Dec 22;12(24):24651-24670. doi: 10.18632/aging.202260. Epub 2020 Dec 22.

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.

Keywords: MYC; biomarkers; distant metastases; gastric carcinogenesis; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome / genetics
  • Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome / metabolism
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor Proteins / genetics
  • Cyclin-Dependent Kinase Inhibitor Proteins / metabolism
  • Down-Regulation
  • Dual-Specificity Phosphatases / genetics
  • Dual-Specificity Phosphatases / metabolism
  • Female
  • Gene Silencing
  • Humans
  • Male
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Middle Aged
  • Peptide Synthases / genetics
  • Peptide Synthases / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-myc / genetics*
  • RNA, Small Interfering
  • RNA-Seq
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4 / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4 / metabolism
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / mortality
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism

Substances

  • Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome
  • CDC16 protein, human
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • MYC protein, human
  • MZT2A protein, human
  • Microtubule-Associated Proteins
  • Proto-Oncogene Proteins c-myc
  • RNA, Small Interfering
  • UBE2T protein, human
  • Ubiquitin-Conjugating Enzymes
  • CDKN3 protein, human
  • Dual-Specificity Phosphatases
  • PTPRA protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4
  • Peptide Synthases
  • TTLL12 protein, human