【佳學(xué)基因檢測(cè)】基于 NMR 的代謝組學(xué)分析確定了 RON-DEK-β-連環(huán)蛋白依賴(lài)性代謝途徑和對(duì)乳腺癌患者生存進(jìn)行分層的基因特征

基因突變?cè)趺粗委熋貨Q

課題調(diào)研《腫瘤突變基因檢測(cè)與個(gè)性化治療方案的制定》《PLoS One》在.?2022 Sep 6;17(9):e0274128.發(fā)表了一篇題目為《基于 NMR 的代謝組學(xué)分析確定了 RON-DEK-β-連環(huán)蛋白依賴(lài)性代謝途徑和對(duì)乳腺癌患者生存進(jìn)行分層的基因特征》腫瘤靶向藥物治療基因檢測(cè)臨床研究文章。該研究由Sara Vicente-Mu?oz,?Brian G Hunt,?Taylor E Lange,?Susanne I Wells,?Susan E Waltz等完成。促進(jìn)了腫瘤的正確治療與個(gè)性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測(cè)與分析的重要性。

腫瘤靶向藥物及正確治療臨床研究?jī)?nèi)容關(guān)鍵詞：

腫瘤靶向治療基因檢測(cè)臨床應(yīng)用結(jié)果

背景：檢測(cè)技術(shù)和治療的進(jìn)步提高了早期乳腺癌的診斷率；然而，所有乳腺癌亞型都會(huì)發(fā)生反復(fù)，并且反復(fù)性和新發(fā)轉(zhuǎn)移通常都具有治療抗性。越來(lái)越多的證據(jù)支持代謝可塑性驅(qū)動(dòng)癌癥反復(fù)的觀點(diǎn)。 RON 和 DEK 是促進(jìn)癌癥轉(zhuǎn)移并在機(jī)械上協(xié)同激活 β-連環(huán)蛋白的蛋白質(zhì)，但代謝后果尚不清楚。方法：為了確定 RON-DEK-β-連環(huán)蛋白依賴(lài)性代謝途徑，我們利用基于 NMR 的代謝組學(xué)方法來(lái)確定代謝物的穩(wěn)態(tài)水平。我們還研究了改變的代謝途徑基因表達(dá)對(duì)乳腺癌患者無(wú)反復(fù)和無(wú)遠(yuǎn)處轉(zhuǎn)移生存的預(yù)后能力的影響，并發(fā)現(xiàn)了可能與反復(fù)相關(guān)的代謝特征。結(jié)果：RON-DEK-β-連環(huán)蛋白丟失顯示出一致的代謝物調(diào)節(jié)琥珀酸和磷酸肌酸。在培養(yǎng)基葡萄糖消耗、乳酸分泌、乙酸分泌以及細(xì)胞內(nèi)谷氨酰胺和谷胱甘肽水平中發(fā)現(xiàn)了 RON 和 DEK 損失（但不是 β-連環(huán)蛋白）之間一致的代謝物改變。僅在細(xì)胞內(nèi)乳酸水平中發(fā)現(xiàn) RON 和 β-連環(huán)蛋白丟失（而不是 DEK）之間一致的代謝物改變。其他途徑命中包括 β-連環(huán)蛋白，包括糖酵解、糖基化、TCA 循環(huán)/回補(bǔ)、NAD+ 產(chǎn)生和肌酸動(dòng)力學(xué)。這些通路中對(duì) RON-DEK-β-catenin 上位性的基因被用來(lái)定義預(yù)測(cè)乳腺癌患者生存和對(duì)化療反應(yīng)的基因特征。結(jié)論：RON-DEK-β-catenin 軸調(diào)節(jié)具有顯著關(guān)聯(lián)的眾多代謝途徑對(duì)乳腺癌患者的結(jié)果。

腫瘤發(fā)生與反復(fù)轉(zhuǎn)移國(guó)際數(shù)據(jù)庫(kù)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.