A Plasma-Derived Protein-Metabolite Multiplexed Panel for Early-Stage Pancreatic Cancer.
A Plasma-Derived Protein-Metabolite Multiplexed Panel for Early-Stage Pancreatic Cancer.
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DOI：
10.1093/jnci/djy126
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发表时间：
2019-04-01
期刊：
影响因子：
--
通讯作者：
Hanash S
中科院分区：
文献类型：
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作者：
Fahrmann JF;Bantis LE;Capello M;Scelo G;Dennison JB;Patel N;Murage E;Vykoukal J;Kundnani DL;Foretova L;Fabianova E;Holcatova I;Janout V;Feng Z;Yip-Schneider M;Zhang J;Brand R;Taguchi A;Maitra A;Brennan P;Max Schmidt C;Hanash S
我们应用培训和测试方法来开发和验证用于检测早期胰腺导管腺癌（PDAC）的血浆代谢物组，以及与先前验证的用于早期PDAC的蛋白质组相结合。一个全面的代谢组学平台最初应用于从20个PDAC病例和80个对照收集的血浆。根据第二个独立队列筛选候选标志物，该队列包括9例浸润性导管内乳头状粘液性肿瘤病例和51例良性胰腺囊肿。在由39例可切除的PDAC病例和82例匹配的健康对照组成的独立测试队列中对所得代谢物组进行盲态验证。评价了将代谢物组与先前验证的蛋白质组组合的附加值。基于过滤标准，选择五种代谢物（乙酰精脒、二乙酰精胺、吲哚衍生物和两种溶血磷脂酰胆碱）作为一组。使用训练集开发了用于区分PDAC和健康对照的组合规则。在早期PDAC样品和对照的盲态验证研究中，5种代谢产物的曲线下面积（AUC）范围为0.726 - 0.842，合并代谢产物模型的AUC为0.892（95%置信区间[CI] = 0.828 - 0.956）。通过将代谢物组与先前验证的由CA 19-9、LRG 1和TIMP 1组成的蛋白质标志物组相结合，性能进一步得到统计学显著改善（AUC = 0.924，95% CI = 0.864至0.983，比较DeLong检验单侧P= 0.02）。与单独的蛋白质组相比，代谢物组与CA 19 -9、TIMP 1和LRG 1组合在早期PDAC的检测中表现出显著改善的性能。
We applied a training and testing approach to develop and validate a plasma metabolite panel for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC) alone and in combination with a previously validated protein panel for early-stage PDAC. A comprehensive metabolomics platform was initially applied to plasmas collected from 20 PDAC cases and 80 controls. Candidate markers were filtered based on a second independent cohort that included nine invasive intraductal papillary mucinous neoplasm cases and 51 benign pancreatic cysts. Blinded validation of the resulting metabolite panel was performed in an independent test cohort consisting of 39 resectable PDAC cases and 82 matched healthy controls. The additive value of combining the metabolite panel with a previously validated protein panel was evaluated. Five metabolites (acetylspermidine, diacetylspermine, an indole-derivative, and two lysophosphatidylcholines) were selected as a panel based on filtering criteria. A combination rule was developed for distinguishing between PDAC and healthy controls using the Training Set. In the blinded validation study with early-stage PDAC samples and controls, the five metabolites yielded areas under the curve (AUCs) ranging from 0.726 to 0.842, and the combined metabolite model yielded an AUC of 0.892 (95% confidence interval [CI] = 0.828 to 0.956). Performance was further statistically significantly improved by combining the metabolite panel with a previously validated protein marker panel consisting of CA 19–9, LRG1, and TIMP1 (AUC = 0.924, 95% CI = 0.864 to 0.983, comparison DeLong test one-sided P= .02). A metabolite panel in combination with CA19-9, TIMP1, and LRG1 exhibited substantially improved performance in the detection of early-stage PDAC compared with a protein panel alone.
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影响因子：
3.7
作者：
Nolen BM;Brand RE;Prosser D;Velikokhatnaya L;Allen PJ;Zeh HJ;Grizzle WE;Huang Y;Lomakin A;Lokshin AE
通讯作者：
Lokshin AE
影响因子：
--
作者：
Mehta KY;Wu HJ;Menon SS;Fallah Y;Zhong X;Rizk N;Unger K;Mapstone M;Fiandaca MS;Federoff HJ;Cheema AK
通讯作者：
Cheema AK
DOI：
10.1158/1078-0432.ccr-14-0365
发表时间：
2015-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
O'Brien DP;Sandanayake NS;Jenkinson C;Gentry-Maharaj A;Apostolidou S;Fourkala EO;Camuzeaux S;Blyuss O;Gunu R;Dawnay A;Zaikin A;Smith RC;Jacobs IJ;Menon U;Costello E;Pereira SP;Timms JF
通讯作者：
Timms JF
DOI：
10.1038/nrgastro.2013.49
发表时间：
2013-07
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
通讯作者：
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影响因子：
4.8
作者：
Rhodes, DR;Yu, JJ;Chinnaiyan, AM
通讯作者：
Chinnaiyan, AM