Downregulated genes by silencing MYC pathway identified with RNA-SEQ analysis as potential prognostic biomarkers in gastric adenocarcinoma.
Downregulated genes by silencing MYC pathway identified with RNA-SEQ analysis as potential prognostic biomarkers in gastric adenocarcinoma.
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通过沉默MYC途径下调的基因通过RNA-SEQ分析鉴定为胃腺癌中潜在的预后生物标志物。
DOI：
10.18632/aging.202260
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发表时间：
2020-12-22
期刊：
影响因子：
--
通讯作者：
Mário Rodriguez Burbano R
中科院分区：
文献类型：
--
作者：
Heitor da Silva Maués J;Ferreira Ribeiro H;de Maria Maués Sacramento R;Maia de Sousa R;Pereira de Tommaso R;Dourado Kovacs Machado Costa B;Cardoso Soares P;Pimentel Assumpção P;de Fátima Aquino Moreira-Nunes C;Mário Rodriguez Burbano R
MYC过度表达是胃癌发生过程中的一种普遍现象。在这项研究中，我们确定了差异表达的基因与胃癌（GC）细胞系沉默MYC下调的配置文件。采用qRT-PCR、western blot和免疫组化方法检测213例弥漫性和肠型胃癌组织中TTLL 12、CDKN 3、CDC 16、PTPRA、MZT 2B、UBE 2 T基因的表达。我们发现高水平的TTLL 12、MZT 2B、CDC 16、UBE 2 T与早期和晚期、淋巴结、远处转移和危险因素如H.幽门螺杆菌。我们的研究结果表明，在弥漫性胃癌中，CDC 16和UBE 2 T的过表达表明预后不良的标志物高于TTLL 12。也就是说，这两种基因过表达的患者比TTLL 12过表达的患者活得更短。在肠GC中，过表达CDC 16的患者的生存率显著低于过表达MZT 2B和UBE 2 T的患者，表明在我们的数据中，与其他两种基因相比，CDC 16的预后价值更差。PTPRA和CDKN 3被证明是重要的评估肿瘤进展的早期和晚期阶段。总之，在这项研究中，我们确定了MYC控制下的GC的诊断和预后生物标志物，与细胞周期和肿瘤过程相关。
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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