A new panel of pancreatic cancer biomarkers discovered using a mass spectrometry-based pipeline.
A new panel of pancreatic cancer biomarkers discovered using a mass spectrometry-based pipeline.
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DOI：
10.1038/bjc.2017.365
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发表时间：
2017-12-05
影响因子：
8.8
通讯作者：
Yang P
中科院分区：
文献类型：
--
作者：
Liu X;Zheng W;Wang W;Shen H;Liu L;Lou W;Wang X;Yang P
胰腺癌是一种侵袭性恶性肿瘤，缺乏早期发现的策略。本研究旨在开发一种连贯、高通量和非歧视性的管道，用于发现新的PC临床生物标志物。我们结合质谱（MS）密集型方法，如等压标签进行相对定量和绝对定量，二维液相色谱-串联质谱（iTRAQ-2DLC-MS/MS）， 1d靶向LC-MS/MS， prime MRM （P-MRM）和基于稳定同位素稀释的MRM (sidd -MRM)，分析健康人（正常对照，NC），良性疾病患者（BD）和PC患者的血清样本，以鉴定PC的新生物标志物。基于新开发的管道，我们在100份血清样本中鉴定了bb101000个蛋白，验证了142个差异表达蛋白，并最终针对4个蛋白进行了绝对定量。新型载脂蛋白E （APOE）、α -胰蛋白酶抑制剂重链H3 （ITIH3）、载脂蛋白A-I （APOA1）、载脂蛋白L1 （APOL1）生物标志物组合与CA19-9联合诊断PC的敏感性（95%）和特异性（94.1%）均有统计学显著提高，优于单独CA19-9。我们开发了一个高效的生物标志物发现、验证和验证管道，每一步都系统地通知下一步。发现了一组可能与PC临床相关的生物标志物的蛋白质。
Pancreatic carcinoma (PC) is an aggressive malignancy that lacks strategies for early detection. This study aimed to develop a coherent, high-throughput and non-discriminatory pipeline for the novel clinical biomarker discovery of PC. We combined mass spectrometry (MS)-intensive methods such as isobaric tags for relative and absolute quantitation with two-dimensional liquid chromatography-tandem mass spectrometry (iTRAQ-2DLC-MS/MS), 1D-targeted LC-MS/MS, prime MRM (P-MRM) and stable isotope dilution-based MRM (SID-MRM) to analyse serum samples from healthy people (normal control, NC), patients with benign diseases (BD) and PC patients to identify novel biomarkers of PC. On the basis of the newly developed pipeline, we identified >1000 proteins, verified 142 differentially expressed proteins and finally targeted four proteins for absolute quantitation in 100 serum samples. The novel biomarker panel of apolipoprotein E (APOE), inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3), apolipoprotein A-I (APOA1), apolipoprotein L1 (APOL1), combining with CA19-9, statistically-significantly improved the sensitivity (95%) and specificity (94.1%), outperforming CA19-9 alone, for the diagnosis of PC. We developed a highly efficient pipeline for biomarker discovery, verification and validation, with each step systematically informing the next. A panel of proteins that might be clinically relevant biomarkers for PC was found.
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影响因子：
7
作者：
Kennedy, Jacob J.;Yan, Ping;Paulovich, Amanda G.
通讯作者：
Paulovich, Amanda G.
DOI：
10.1038/ajg.2016.482
发表时间：
2017-01
期刊：
The American journal of gastroenterology
影响因子：
--
作者：
Kaur S;Smith LM;Patel A;Menning M;Watley DC;Malik SS;Krishn SR;Mallya K;Aithal A;Sasson AR;Johansson SL;Jain M;Singh S;Guha S;Are C;Raimondo M;Hollingsworth MA;Brand RE;Batra SK
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Batra SK
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
7
作者：
Ross, PL;Huang, YLN;Pappin, DJ
通讯作者：
Pappin, DJ
影响因子：
2.2
作者：
Kaur S;Baine MJ;Jain M;Sasson AR;Batra SK
通讯作者：
Batra SK