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腾讯登录Nat Med：特殊氨基酸水平的变化或可帮助进行早期的胰腺癌发病诊断
| 导读 | 近日，来自美国达纳-法伯癌症研究所(Dana-Farber Cancer Institute)等处的研究人员通过研究发现了胰腺癌发生早期的迹象，即在疾病被诊断和症状出现前某些特殊氨基酸的水平会上涨，相关研究刊登于国际著名杂志Nature Medicine上。 |
近日，来自美国达纳-法伯癌症研究所(Dana-Farber Cancer Institute)等处的研究人员通过研究发现了胰腺癌发生早期的迹象，即在疾病被诊断和症状出现前某些特殊氨基酸的水平会上涨，相关研究刊登于国际著名杂志Nature Medicine上。
文章中，研究者Brian Wolpin表示，许多胰腺导管腺癌（PDAC）患者都是在疾病发展到晚期的时候才被诊断出来，在疾病发生阶段对其进行快速准确的检测或可有效帮助改善患者的治疗结果，这项研究中我们就去研究揭示是否胰腺导管腺癌会发生一些代谢变化，即机体利用能量和营养物的差别，从而帮助进行疾病的快速诊断。
研究者收集了1500名参与者的血液样本，并对这些样本中100多种不同的代谢产物进行分析，随后对胰腺癌患者和非癌症患者的研究结果进行对比。Wolpin表示，相比未患胰腺癌的患者来讲，胰腺癌患者机体中的支链氨基酸水平非常高，支链氨基酸是氨基酸的一种，也是构筑蛋白质的主要成分。
本文的研究结果或许可以帮助研究人员假设，是否支链氨基酸水平的升高可以作为早期胰腺癌的预测诊断；实验结果显示新发胰腺癌的小鼠机体中支链氨基酸水平的水平也出现了异常升高的现象。最后研究者说道，研究结果或许可以帮助科学家们揭示胰腺癌肿瘤如何与患者机体的正常组织进行相互作用；为深入理解胰腺癌改变人体机体代谢的路径提供一定的思路，当然为后期开发治疗胰腺癌的新型靶向疗法会提供新的思路和线索。
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转化医学网推荐的原文摘要：
Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development
Nature Medicine doi:10.1038/nm.3686
Jared R Mayers, Chen Wu, Clary B Clish, Peter Kraft, Margaret E Torrence, Brian P Fiske, Chen Yuan, Ying Bao, Mary K Townsend, Shelley S Tworoger, Shawn M Davidson, Thales Papagiannakopoulos, Annan Yang, Talya L Dayton, Shuji Ogino, Meir J Stampfer, Edward L Giovannucci, Zhi Rong Qian, Douglas A Rubinson, Jing Ma, Howard D Sesso, John M Gaziano, Barbara B Cochrane, Simin Liu, Jean Wactawski-Wende et al.
Most patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and survive less than 12 months1. PDAC has been linked with obesity and glucose intolerance2, 3, 4, but whether changes in circulating metabolites are associated with early cancer progression is unknown. To better understand metabolic derangements associated with early disease, we profiled metabolites in prediagnostic plasma from individuals with pancreatic cancer (cases) and matched controls from four prospective cohort studies. We find that elevated plasma levels of branched-chain amino acids (BCAAs) are associated with a greater than twofold increased risk of future pancreatic cancer diagnosis. This elevated risk was independent of known predisposing factors, with the strongest association observed among subjects with samples collected 2 to 5 years before diagnosis, when occult disease is probably present. We show that plasma BCAAs are also elevated in mice with early-stage pancreatic cancers driven by mutant Kras expression but not in mice with Kras-driven tumors in other tissues, and that breakdown of tissue protein accounts for the increase in plasma BCAAs that accompanies early-stage disease. Together, these findings suggest that increased whole-body protein breakdown is an early event in development of PDAC.
Nature Medicine doi:10.1038/nm.3686
Jared R Mayers, Chen Wu, Clary B Clish, Peter Kraft, Margaret E Torrence, Brian P Fiske, Chen Yuan, Ying Bao, Mary K Townsend, Shelley S Tworoger, Shawn M Davidson, Thales Papagiannakopoulos, Annan Yang, Talya L Dayton, Shuji Ogino, Meir J Stampfer, Edward L Giovannucci, Zhi Rong Qian, Douglas A Rubinson, Jing Ma, Howard D Sesso, John M Gaziano, Barbara B Cochrane, Simin Liu, Jean Wactawski-Wende et al.
Most patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and survive less than 12 months1. PDAC has been linked with obesity and glucose intolerance2, 3, 4, but whether changes in circulating metabolites are associated with early cancer progression is unknown. To better understand metabolic derangements associated with early disease, we profiled metabolites in prediagnostic plasma from individuals with pancreatic cancer (cases) and matched controls from four prospective cohort studies. We find that elevated plasma levels of branched-chain amino acids (BCAAs) are associated with a greater than twofold increased risk of future pancreatic cancer diagnosis. This elevated risk was independent of known predisposing factors, with the strongest association observed among subjects with samples collected 2 to 5 years before diagnosis, when occult disease is probably present. We show that plasma BCAAs are also elevated in mice with early-stage pancreatic cancers driven by mutant Kras expression but not in mice with Kras-driven tumors in other tissues, and that breakdown of tissue protein accounts for the increase in plasma BCAAs that accompanies early-stage disease. Together, these findings suggest that increased whole-body protein breakdown is an early event in development of PDAC.
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