Identification of IGFBP2 and IGFBP3 As Compensatory Biomarkers for CA19-9 in Early-Stage Pancreatic Cancer Using a Combination of Antibody-Based and LC-MS/MS-Based Proteomics

被引：81

作者：

Yoneyama, Toshihiro ^{[1
]}

Ohtsuki, Sumio ^{[2
,4
]}

Honda, Kazufumi ^{[3
,4
]}

Kobayashi, Makoto ^{[3
]}

Iwasaki, Motoki ^{[5
]}

Uchida, Yasuo ^{[1
]}

Okusaka, Takuji ^{[6
]}

Nakamori, Shoji ^{[7
]}

Shimahara, Masashi ^{[8
]}

Ueno, Takaaki ^{[8
]}

Tsuchida, Akihiko ^{[9
]}

Sata, Naohiro ^{[10
]}

Ioka, Tatsuya ^{[11
]}

Yasunami, Yohichi ^{[12
]}

Kosuge, Tomoo ^{[13
]}

Kaneda, Takashi ^{[14
]}

Kato, Takao ^{[15
]}

Yagihara, Kazuhiro ^{[16
]}

Fujita, Shigeyuki ^{[17
]}

Huang, Wilber ^{[18
]}

Yamada, Tesshi ^{[3
]}

Tachikawa, Masanori ^{[1
]}

Terasaki, Tetsuya ^{[1
]}

机构：

[1] Tohoku Univ, Grad Sch Pharmaceut Sci, Div Membrane Transport & Drug Targeting, Sendai, Miyagi, Japan

[2] Kumamoto Univ, Dept Pharmaceut Microbiol, Fac Life Sci, Kumamoto, Japan

[3] Natl Canc Ctr, Div Chemotherapy & Clin Res, Res Inst, Tokyo, Japan

[4] Japan Agcy Med Res & Dev AMED CREST, Tokyo, Japan

[5] Natl Canc Ctr, Div Epidemiol, Res Ctr Canc Prevent & Screening, Tokyo, Japan

[6] Natl Canc Ctr, Dept Hepatobiliary & Pancreat Oncol, Tokyo, Japan

[7] Natl Hosp Org, Osaka Natl Hosp, Dept Hepatobiliary Pancreat Surg, Osaka, Japan

[8] Osaka Med Coll, Dept Oral Surg, Osaka, Japan

[9] Tokyo Med Univ, Dept Gastrointestinal & Pediat Surg, Tokyo, Japan

[10] Jichi Med Univ, Dept Surg, Shimotsuke, Tochigi, Japan

[11] Osaka Med Ctr Canc & Cardiovasc Dis, Dept Hepatobiliary & Pancreat Oncol, Osaka, Japan

[12] Fukuoka Univ, Islet Inst, Fukuoka, Japan

[13] Natl Canc Ctr, Hepatobiliary & Pancreat Surg Div, Tokyo, Japan

[14] Nihon Univ, Sch Dent Matsudo, Dept Radiol, Chiba, Japan

[15] Nihon Univ, Sch Dent Matsudo, Dept Oral Implant, Chiba, Japan

[16] Saitama Canc Ctr, Dept Oral Surg, Saitama, Japan

[17] Wakayama Med Univ, Dept Oral & Maxillofacial Surg, Wakayama, Japan

[18] Abnova, Taipei, Taiwan

来源：

PLOS ONE | 2016年 / 11卷 / 08期

关键词：

BINDING-PROTEINS; PLASMA BIOMARKER; INSULIN; SERUM; RISK; DISCOVERY; QUANTITATION; FLUIDS; ASSAY; PATH;

D O I：

10.1371/journal.pone.0161009

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Pancreatic cancer is one of the most lethal tumors, and reliable detection of early-stage pancreatic cancer and risk diseases for pancreatic cancer is essential to improve the prognosis. As 260 genes were previously reported to be upregulated in invasive ductal adenocarcinoma of pancreas (IDACP) cells, quantification of the corresponding proteins in plasma might be useful for IDACP diagnosis. Therefore, the purpose of the present study was to identify plasma biomarkers for early detection of IDACP by using two proteomics strategies: antibody-based proteomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics. Among the 260 genes, we focused on 130 encoded proteins with known function for which antibodies were available. Twenty-three proteins showed values of the area under the curve (AUC) of more than 0.8 in receiver operating characteristic (ROC) analysis of reverse-phase protein array (RPPA) data of IDACP patients compared with healthy controls, and these proteins were selected as biomarker candidates. We then used our high-throughput selected reaction monitoring or multiple reaction monitoring (SRM/MRM) methodology, together with an automated sample preparation system, micro LC and auto analysis system, to quantify these candidate proteins in plasma from healthy controls and IDACP patients on a large scale. The results revealed that insulin-like growth factor- binding protein (IGFBP) 2 and IGFBP3 have the ability to discriminate IDACP patients at an early stage from healthy controls, and IGFBP2 appeared to be increased in risk diseases of pancreatic malignancy, such as intraductal papillary mucinous neoplasms (IPMNs). Furthermore, diagnosis of IDACP using the combination of carbohydrate antigen 19-9 (CA19-9), IGFBP2 and IGFBP3 is significantly more effective than CA19-9 alone. This suggests that IGFBP2 and IGFBP3 may serve as compensatory biomarkers for CA19-9. Early diagnosis with this marker combination may improve the prognosis of IDACP patients.

引用

页数：23

共 57 条

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