O-Glycan-Altered Extracellular Vesicles: A Specific Serum Marker Elevated in Pancreatic Cancer

被引：27

作者：

Yokose, Takahiro ^{[1
]}

Kabe, Yasuaki ^{[2
]}

Matsuda, Atsushi ^{[2
]}

Kitago, Minoru ^{[1
]}

Matsuda, Sachiko ^{[1
]}

Hirai, Miwa ^{[2
]}

Nakagawa, Tomomi ^{[2
]}

Masugi, Yohei ^{[3
]}

Hishiki, Takako ^{[2
]}

Nakamura, Yuki ^{[1
]}

Shinoda, Masahiro ^{[1
]}

Yagi, Hiroshi ^{[1
]}

Abe, Yuta ^{[1
]}

Oshima, Go ^{[1
]}

Hori, Shutaro ^{[1
]}

Nakano, Yutaka ^{[1
]}

Honda, Kazufumi ^{[4
,5
]}

Kashiro, Ayumi ^{[4
]}

Morizane, Chigusa ^{[6
]}

Nara, Satoshi ^{[7
]}

Kikuchi, Shojiro ^{[8
]}

Shibahara, Takahiko ^{[9
]}

Itonaga, Makoto ^{[10
]}

Ono, Masayuki ^{[10
]}

Minegishi, Naoko ^{[11
]}

Koshiba, Seizo ^{[11
,12
]}

Yamamoto, Masayuki ^{[11
,13
]}

Kuno, Atsushi ^{[14
]}

Handa, Hiroshi ^{[15
]}

Sakamoto, Michiie ^{[3
]}

Suematsu, Makoto ^{[2
]}

Kitagawa, Yuko ^{[1
]}

机构：

[1] Keio Univ, Dept Surg, Sch Med, Tokyo 1608582, Japan

[2] Keio Univ, Dept Biochem, Sch Med, Tokyo 1608582, Japan

[3] Keio Univ, Dept Pathol, Sch Med, Tokyo 1608582, Japan

[4] Natl Canc Ctr, Dept Biomarkers Early Detect Canc, Res Inst, Tokyo 1040045, Japan

[5] Nippon Med Sch, Grad Sch Med, Dept Bioregulat, Tokyo 1138602, Japan

[6] Natl Canc Ctr, Dept Hepatobiliary & Pancreat Oncol, Tokyo 1040045, Japan

[7] Natl Canc Ctr, Dept Hepatobiliary & Pancreat Surg, Tokyo 1040045, Japan

[8] Hyogo Coll Med, Inst Adv Med Sci, Nishinomiya, Hyogo 6638501, Japan

[9] Tokyo Dent Coll, Dept Oral & Maxillofacial Surg, Tokyo 1028159, Japan

[10] JVCKENWOOD Corp, Healthcare Business Div, Yokosuka, Kanagawa 2398520, Japan

[11] Tohoku Univ, Tohoku Med Megabank Org, Aoba Ku, 2-1 Seiryo Machi, Sendai, Miyagi 9808573, Japan

[12] Tohoku Univ, Adv Res Ctr Innovat Next Generat Med, Aoba Ku, 2-1 Seiryo Machi, Sendai, Miyagi 9808573, Japan

[13] Tohoku Univ, Grad Sch Med, Aoba Ku, 2-1 Seiryo Machi, Sendai, Miyagi 9808575, Japan

[14] Natl Inst Adv Ind Sci & Technol, Biotechnol Res Inst Drug Discovery, Tsukuba, Ibaraki 3058565, Japan

[15] Tokyo Med Univ, Dept Biol Chem, Tokyo 1600023, Japan

来源：

CANCERS | 2020年 / 12卷 / 09期

关键词：

extracellular vesicles; lectin microarray; pancreatic cancer; liquid biopsy; O-glycan; glycomics; FINE-NEEDLE-ASPIRATION; ASSISTED LECTIN MICROARRAY; EXOSOMES; GLYCOSYLATION; MALIGNANCY; MANAGEMENT; DIAGNOSIS; STRATEGY; BIOPSY;

D O I：

10.3390/cancers12092469

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary Pancreatic cancer (PC) is among the most lethal malignancies due to an often delayed and difficult initial diagnosis. Therefore, the development of a novel, early stage, diagnostic PC marker in liquid biopsies is of great significance. In this study, we analyzed the differential glycomic profiling of extracellular vesicles (EVs) derived from serum using lectin microarray. The glyco-candidates of PC-specific EVs were quantified using a high-sensitive exosome-counting system, ExoCounter. An absolute quantification system for altered glycan-containing EVs elevated in PC serum was established. EVs recognized byO-glycan-binding lectins ABA or ACA were identified as candidate markers by lectin microarray. Quantitative analyses using ExoCounter revealed that the ABA- or ACA-positive EVs were significantly increased in the serum of PC patients. These specific EVs with O-glycans can act as potential biomarkers in a liquid biopsy for PC patients screening. Pancreatic cancer (PC) is among the most lethal malignancies due to an often delayed and difficult initial diagnosis. Therefore, the development of a novel, early stage, diagnostic PC marker in liquid biopsies is of great significance. In this study, we analyzed the differential glycomic profiling of extracellular vesicles (EVs) derived from serum (two cohorts including 117 PC patients and 98 normal controls) using lectin microarray. The glyco-candidates of PC-specific EVs were quantified using a high-sensitive exosome-counting system, ExoCounter. An absolute quantification system for altered glycan-containing EVs elevated in PC serum was established. EVs recognized byO-glycan-binding lectins ABA or ACA were identified as candidate markers by lectin microarray. Quantitative analyses using ExoCounter revealed that the ABA- or ACA-positive EVs were significantly increased in the culture of PC cell lines or in the serum of PC patients including carbohydrate antigen 19-9 negative patients with high area under curve values. The elevated numbers of EVs in PC serum returned to normal levels after pancreatectomy. Histological examination confirmed that the tumors stained with ABA/ACA. These specific EVs withO-glycans recognized by ABA/ACA are elevated in PC sera and can act as potential biomarkers in a liquid biopsy for PC patients screening.

引用

页码：1 / 17

页数：17

共 45 条

[1] The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal [J].

Ballehaninna, Umashankar K. ;

Chamberlain, Ronald S. .

JOURNAL OF GASTROINTESTINAL ONCOLOGY, 2012, 3 (02) :105-119

[2] Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles [J].

Colombo, Marina ;

Raposo, Graca ;

Thery, Clotilde .

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 30, 2014, 30 :255-289

[3] More efficient induction of HLA-A*0201-restricted and carcinoembryonic antigen (CEA)-specific CTL response by immunization with exosomes prepared from heat-stressed CEA-positive tumor cells [J].

Dai, SM ;

Wan, T ;

Wang, BM ;

Zhou, XY ;

Xiu, FM ;

Chen, TY ;

Wu, YF ;

Cao, XT .

CLINICAL CANCER RESEARCH, 2005, 11 (20) :7554-7563

[4] Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 [J].

Ferlay, Jacques ;

Shin, Hai-Rim ;

Bray, Freddie ;

Forman, David ;

Mathers, Colin ;

Parkin, Donald Maxwell .

INTERNATIONAL JOURNAL OF CANCER, 2010, 127 (12) :2893-2917

[5] Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma [J].

Ferrone, Cristina R. ;

Finkelstein, Dianne M. ;

Thayer, Sarah P. ;

Muzikansky, Alona ;

Fernandez-del Castillo, Carlos ;

Warshaw, Andrew L. .

JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (18) :2897-2902

[6]

Fritscher-Ravens A, 2002, AM J GASTROENTEROL, V97, P2768

[7]

Fukuda M, 1996, CANCER RES, V56, P2237

[8] Glycosylation defining cancer malignancy: New wine in an old bottle [J].

Hakomori, S .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (16) :10231-10233

[9] Concept, strategy and realization of lectin-based glycan profiling [J].

Hirabayashi, Jun .

JOURNAL OF BIOCHEMISTRY, 2008, 144 (02) :139-147

[10] Tumour exosome integrins determine organotropic metastasis [J].

Hoshino, Ayuko ;

Costa-Silva, Bruno ;

Shen, Tang-Long ;

Rodrigues, Goncalo ;

Hashimoto, Ayako ;

Mark, Milica Tesic ;

Molina, Henrik ;

Kohsaka, Shinji ;

Di Giannatale, Angela ;

Ceder, Sophia ;

Singh, Swarnima ;

Williams, Caitlin ;

Soplop, Nadine ;

Uryu, Kunihiro ;

Pharmer, Lindsay ;

King, Tari ;

Bojmar, Linda ;

Davies, Alexander E. ;

Ararso, Yonathan ;

Zhang, Tuo ;

Zhang, Haiying ;

Hernandez, Jonathan ;

Weiss, Joshua M. ;

Dumont-Cole, Vanessa D. ;

Kramer, Kimberly ;

Wexler, Leonard H. ;

Narendran, Aru ;

Schwartz, Gary K. ;

Healey, John H. ;

Sandstrom, Per ;

Labori, Knut Jorgen ;

Kure, Elin H. ;

Grandgenett, Paul M. ;

Hollingsworth, Michael A. ;

de Sousa, Maria ;

Kaur, Sukhwinder ;

Jain, Maneesh ;

Mallya, Kavita ;

Batra, Surinder K. ;

Jarnagin, William R. ;

Brady, Mary S. ;

Fodstad, Oystein ;

Muller, Volkmar ;

Pantel, Klaus ;

Minn, Andy J. ;

Bissell, Mina J. ;

Garcia, Benjamin A. ;

Kang, Yibin ;

Rajasekhar, Vinagolu K. ;

Ghajar, Cyrus M. .

NATURE, 2015, 527 (7578) :329-+

← 1 2 3 4 5 →