【佳学基因检测】基于 NMR 的代谢组学分析确定了 RON-DEK-β-连环蛋白依赖性代谢途径和对乳腺癌患者生存进行分层的基因特征

基因突变怎么治疗秘决

课题调研《肿瘤突变基因检测与个性化治疗方案的制定》《PLoS One》在. 2022 Sep 6;17(9):e0274128.发表了一篇题目为《基于 NMR 的代谢组学分析确定了 RON-DEK-β-连环蛋白依赖性代谢途径和对乳腺癌患者生存进行分层的基因特征》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Sara Vicente-Muñoz, Brian G Hunt, Taylor E Lange, Susanne I Wells, Susan E Waltz等完成。促进了肿瘤的精准治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤靶向药物及精准治疗临床研究内容关键词：

肿瘤靶向治疗基因检测临床应用结果

背景：检测技术和治疗的进步提高了早期乳腺癌的诊断率；然而，所有乳腺癌亚型都会发生复发，并且复发性和新发转移通常都具有治疗抗性。越来越多的证据支持代谢可塑性驱动癌症复发的观点。 RON 和 DEK 是促进癌症转移并在机械上协同激活 β-连环蛋白的蛋白质，但代谢后果尚不清楚。方法：为了确定 RON-DEK-β-连环蛋白依赖性代谢途径，我们利用基于 NMR 的代谢组学方法来确定代谢物的稳态水平。我们还研究了改变的代谢途径基因表达对乳腺癌患者无复发和无远处转移生存的预后能力的影响，并发现了可能与复发相关的代谢特征。结果：RON-DEK-β-连环蛋白丢失显示出一致的代谢物调节琥珀酸和磷酸肌酸。在培养基葡萄糖消耗、乳酸分泌、乙酸分泌以及细胞内谷氨酰胺和谷胱甘肽水平中发现了 RON 和 DEK 损失（但不是 β-连环蛋白）之间一致的代谢物改变。仅在细胞内乳酸水平中发现 RON 和 β-连环蛋白丢失（而不是 DEK）之间一致的代谢物改变。其他途径命中包括 β-连环蛋白，包括糖酵解、糖基化、TCA 循环/回补、NAD+ 产生和肌酸动力学。这些通路中对 RON-DEK-β-catenin 上位性的基因被用来定义预测乳腺癌患者生存和对化疗反应的基因特征。结论：RON-DEK-β-catenin 轴调节具有显着关联的众多代谢途径对乳腺癌患者的结果。

肿瘤发生与复发转移国际数据库描述：

Background: Advances in detection techniques and treatment have increased the diagnosis of breast cancer at early stages; however, recurrence occurs in all breast cancer subtypes, and both recurrent and de novo metastasis are typically treatment resistant. A growing body of evidence supports the notion that metabolic plasticity drives cancer recurrence. RON and DEK are proteins that promote cancer metastasis and synergize mechanistically to activate β-catenin, but the metabolic consequences are unknown.Methods: To ascertain RON-DEK-β-catenin dependent metabolic pathways, we utilized an NMR-based metabolomics approach to determine steady state levels of metabolites. We also interrogated altered metabolic pathway gene expression for prognostic capacity in breast cancer patient relapse-free and distant metastasis-free survival and discover a metabolic signature that is likely associated with recurrence.Results: RON-DEK-β-catenin loss showed a consistent metabolite regulation of succinate and phosphocreatine. Consistent metabolite alterations between RON and DEK loss (but not β-catenin) were found in media glucose consumption, lactate secretion, acetate secretion, and intracellular glutamine and glutathione levels. Consistent metabolite alterations between RON and β-catenin loss (and not DEK) were found only in intracellular lactate levels. Further pathway hits include β-catenin include glycolysis, glycosylation, TCA cycle/anaplerosis, NAD+ production, and creatine dynamics. Genes in these pathways epistatic to RON-DEK-β-catenin were used to define a gene signature that prognosticates breast cancer patient survival and response to chemotherapy.Conclusions: The RON-DEK-β-catenin axis regulates the numerous metabolic pathways with significant associations to breast cancer patient outcomes.

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