Usefulness of MALDI-TOF/MS Identification of Low-MW Fragments in Sera for the Differential Diagnosis of Pancreatic Cancer

Usefulness of MALDI-TOF/MS Identification of Low-MW Fragments in Sera for the Differential Diagnosis of Pancreatic Cancer
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DOI:
10.1097/mpa.0b013e318273096c
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发表时间:
2013-05-01
期刊:
影响因子:
2.9
通讯作者:
Plebani, Mario
Plebani, Mario
中科院分区:
医学4区
文献类型:
--
作者:
Padoan, Andrea;Seraglia, Roberta;Plebani, Mario

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为了寻找新的胰腺癌(PaCa)生物标志物,我们对22例对照组、51例PaCa、37例慢性胰腺炎、24例II型糖尿病(DM)、29例胃癌(GC)和24例慢性胃炎(CG)患者的血清进行了MALDI-TOF/MS分析。方法:用Sep-Pak C18纯化血清,然后用MALDI-TOF/MS Anchorchip进行分析。结果:在所有光谱中至少有5%的特征被选中(n = 160, m/z范围,1200-5000)。在单因素分析中,2个特征(m/z 2049和2305)与PaCa相关,3个特征(m/z 1449、1605和2006)与DM相关。没有特征与胃癌或慢性胃炎相关。得到十倍交叉验证二递归划分树进行患者分类。该树(CA 19-9,年龄,m/z 2006, 2599, 2753和4997)仅考虑糖尿病患者,允许区分DM[受试者工作特征曲线下面积(AUC), 0.997],慢性胰腺炎(AUC, 0.968)和PaCa (AUC, 0.980),总体正确分类率为89%。该树包括CA 19-9、1550和2937 m/z特征,在区分局部和高级PaCa方面达到了0.970的AUC。MALDI-TOF-TOF分析显示1550特征为Apo-A1片段,确定为全蛋白,与PaCa密切相关。结论:研究结果表明,使用MALDI-TOF/MS鉴定的血清肽在解决PaCa诊断中的作用。
Objectives: To identify new biomarkers of pancreatic cancer (PaCa), we performed MALDI-TOF/MS analysis of sera from 22 controls, 51 PaCa, 37 chronic pancreatitis, 24 type II diabetes mellitus (DM), 29 gastric cancer (GC), and 24 chronic gastritis (CG).Methods: Sera were purified by Sep-Pak C18 before MALDI-TOF/MS Anchorchip analysis.Results: Features present in at least 5% of all spectra were selected (n = 160, m/z range, 1200-5000). At univariate analysis, 2 features (m/z 2049 and 2305) correlated with PaCa, 3 (m/z 1449, 1605, and 2006) with DM. No feature characterized gastric cancer or chronic gastritis. Tenfold cross-validation binary recursive partitioning trees were obtained for patients' classification. The tree (CA 19-9, age, m/z 2006, 2599, 2753, and 4997), built considering only patients with diabetes, allowed a distinction between DM [area under the receiver operating characteristic curve (AUC), 0.997], chronic pancreatitis (AUC, 0.968), and PaCa (AUC, 0.980), with an overall correct classification rate of 89%. The tree including CA 19-9, 1550, and 2937 m/z features, achieved an AUC of 0.970 in distinguishing localized from advanced PaCa. MALDI-TOF-TOF analysis revealed the 1550 feature as a fragment of Apo-A1, which was determined as whole protein and demonstrated to be closely correlated with PaCa.Conclusions: The findings made demonstrate a role for serum peptides identified using MALDI-TOF/MS for addressing PaCa diagnosis.