Identification of highly sensitive biomarkers that can aid the early detection of pancreatic cancer using GC/MS/MS-based targeted metabolomics

被引：40

作者：

Hirata, Yuichi ^{[1
]}

Kobayashi, Takashi ^{[1
]}

Nishiumi, Shin ^{[1
]}

Yamanaka, Kodai ^{[1
]}

Nakagawa, Takashi ^{[1
]}

Fujigaki, Seiji ^{[1
]}

Iemoto, Takao ^{[1
]}

Kobayashi, Makoto ^{[2
]}

Okusaka, Takuji ^{[3
]}

Nakamori, Shoji ^{[4
]}

Shimahara, Masashi ^{[5
]}

Ueno, Takaaki ^{[5
]}

Tsuchida, Akihiko ^{[6
]}

Sata, Naohiro ^{[7
]}

Ioka, Tatsuya ^{[8
]}

Yasunami, Yohichi ^{[9
]}

Kosuge, Tomoo ^{[10
]}

Kaneda, Takashi ^{[11
]}

Kato, Takao ^{[12
]}

Yagihara, Kazuhiro ^{[13
]}

Fujita, Shigeyuki ^{[14
]}

Yamada, Tesshi ^{[2
]}

Honda, Kazufumi ^{[2
,15
]}

Azuma, Takeshi ^{[1
]}

Yoshida, Masaru ^{[1
,16
,17
]}

机构：

[1] Kobe Univ, Dept Internal Med, Grad Sch Med, Div Gastroenterol, Kobe, Hyogo, Japan

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

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

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

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

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

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

[8] Osaka Med Ctr Canc & Cardiovasc Dis, Dept GI Canc Screening & Surveillance, Osaka, Japan

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

[10] JR Tokyo Gen Hosp, Dept Gastrointestinal Surg, Tokyo, Japan

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

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

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

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

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

[16] Kobe Univ, Grad Sch Med, Dept Internal Related, Metab Res, Kobe, Hyogo, Japan

[17] AMED, AMED CREST, Kobe, Hyogo, Japan

来源：

CLINICA CHIMICA ACTA | 2017年 / 468卷

基金：

日本学术振兴会;

关键词：

Biomarker; GC/MS/MS; Pancreatic cancer; Early detection; Metabolomics; SERUM METABOLOMICS; DIAGNOSTIC-APPROACH; HISTIDINE; 1,5-ANHYDROGLUCITOL; PROLIFERATION; EXPRESSION;

D O I：

10.1016/j.cca.2017.02.011

中图分类号：

R446 [实验室诊断]; R-33 [实验医学、医学实验];

学科分类号：

1001 ;

摘要：

Background: To improve prognosis of pancreatic cancer (PC) patients, the discovery of more reliable biomarkers for the early detection is desired. Methods: Blood samples were collected by 2 independent groups. The 1st set was included 55 early PC and 58 healthy volunteers (HV), and the 2nd set was included 16 PC and 16 HV. The 16 targeted metabolites were quantitatively analyzed by gas chromatography/tandem mass spectrometry together with their corresponding stable isotopes. In the 1st set, the levels of these metabolites were evaluated, and diagnostic models were constructed via multivariate logistic regression analysis, leading to validation using the 2nd set. Results: In the 1st set, model X consisting of 4 candidates based on our previous report possessed higher sensitivity (74.1%) than carbohydrate antigen 19-9 (CA19-9). Model Y, consisting of 2 metabolites newly selected from 16 metabolites via stepwise method possessed higher sensitivity (70.4%) than CA19-9. Furthermore, combining model Y with CA19-9 increased its sensitivity (90.7%) and specificity (89.5%). In the 2nd set, combining model Y with CA19-9 displayed high sensitivity (81.3%) and specificity (93.8%). In particular, it displayed very high sensitivity (100%) for resectable PC. Conclusions: Quantitative analysis confirmed that metabolomics-based diagnostic methods are useful for detecting PC early. (C) 2017 Elsevier B.V. All rights reserved.

引用

页码：98 / 104

页数：7

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