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.
Subject(s)
Adenocarcinoma/genetics , Proto-Oncogene Proteins c-myc/genetics , Stomach Neoplasms/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 , RNA, Small Interfering , RNA-Seq , Receptor-Like Protein Tyrosine Phosphatases, Class 4/genetics , Receptor-Like Protein Tyrosine Phosphatases, Class 4/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/mortality , Ubiquitin-Conjugating Enzymes/genetics , Ubiquitin-Conjugating Enzymes/metabolismABSTRACT
BACKGROUND: Approximately 70% of cancer-related deaths occur in low- and middle-income countries. In addition to social and racial inequalities, treatment options in these countries are usually limited because of the lack of trained staff and equipment, limited patient access to health services, and a small number of clinical guidelines. OBJECTIVES: The Brazilian Society of Surgical Oncology developed this guideline to address these barriers and guide physicians treating patients with endometrial cancer (EC) in regions with limited resources and few specialized centers. METHODS: The guideline was prepared from 10 January to 25 October 20192019 by a multidisciplinary team of 56 experts to discuss the main obstacles faced by EC patients in Brazil. Thirteen questions considered critical to the surgical treatment of these patients were defined. The questions were assigned to groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments for presentations in meetings, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including staging, fertility spearing treatment, genetic testing, sentinel lymph node use, surgical treatment, and other clinical relevant questions, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSIONS: It is possible to provide adequate treatment for most EC patients in resource-limited areas, but the first option should be referral to specialized centers with more resources.
