O-glycan-altered extracellular vesicles: A specific serum marker elevated in pancreatic cancer

Takahiro Yokose; Yasuaki Kabe; Atsushi Matsuda; Minoru Kitago; Sachiko Matsuda; Miwa Hirai; Tomomi Nakagawa; Yohei Masugi; Takako Hishiki; Yuki Nakamura; Masahiro Shinoda; Hiroshi Yagi; Yuta Abe; Go Oshima; Shutaro Hori; Yutaka Nakano; Kazufumi Honda; Ayumi Kashiro; Chigusa Morizane; Satoshi Nara; Shojiro Kikuchi; Takahiko Shibahara; Makoto Itonaga; Masayuki Ono; Naoko Minegishi; Seizo Koshiba; Masayuki Yamamoto; Atsushi Kuno; Hiroshi Handa; Michiie Sakamoto; Makoto Suematsu; Yuko Kitagawa

doi:10.3390/cancers12092469

O-glycan-altered extracellular vesicles: A specific serum marker elevated in pancreatic cancer

Takahiro Yokose, Yasuaki Kabe, Atsushi Matsuda, Minoru Kitago, Sachiko Matsuda, Miwa Hirai, Tomomi Nakagawa, Yohei Masugi, Takako Hishiki, Yuki Nakamura, Masahiro Shinoda, Hiroshi Yagi, Yuta Abe, Go Oshima, Shutaro Hori, Yutaka Nakano, Kazufumi Honda, Ayumi Kashiro, Chigusa Morizane, Satoshi NaraShojiro Kikuchi, Takahiko Shibahara, Makoto Itonaga, Masayuki Ono, Naoko Minegishi, Seizo Koshiba, Masayuki Yamamoto, Atsushi Kuno, Hiroshi Handa, Michiie Sakamoto, Makoto Suematsu, Yuko Kitagawa

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

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 by O-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 with O-glycans recognized by ABA/ACA are elevated in PC sera and can act as potential biomarkers in a liquid biopsy for PC patients screening.

Original language	English
Article number	2469
Pages (from-to)	1-17
Number of pages	17
Journal	Cancers
Volume	12
Issue number	9
DOIs	https://doi.org/10.3390/cancers12092469
Publication status	Published - 2020 Sept

Keywords

Extracellular vesicles
Glycomics
Lectin microarray
Liquid biopsy
O-glycan
Pancreatic cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers12092469

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Yokose, T., Kabe, Y., Matsuda, A., Kitago, M., Matsuda, S., Hirai, M., Nakagawa, T., Masugi, Y., Hishiki, T., Nakamura, Y., Shinoda, M., Yagi, H., Abe, Y., Oshima, G., Hori, S., Nakano, Y., Honda, K., Kashiro, A., Morizane, C., ... Kitagawa, Y. (2020). O-glycan-altered extracellular vesicles: A specific serum marker elevated in pancreatic cancer. Cancers, 12(9), 1-17. Article 2469. https://doi.org/10.3390/cancers12092469

@article{528619977e8641f5893ab99e77a18441,

title = "O-glycan-altered extracellular vesicles: A specific serum marker elevated in pancreatic cancer",

abstract = "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 by O-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 with O-glycans recognized by ABA/ACA are elevated in PC sera and can act as potential biomarkers in a liquid biopsy for PC patients screening.",

keywords = "Extracellular vesicles, Glycomics, Lectin microarray, Liquid biopsy, O-glycan, Pancreatic cancer",

author = "Takahiro Yokose and Yasuaki Kabe and Atsushi Matsuda and Minoru Kitago and Sachiko Matsuda and Miwa Hirai and Tomomi Nakagawa and Yohei Masugi and Takako Hishiki and Yuki Nakamura and Masahiro Shinoda and Hiroshi Yagi and Yuta Abe and Go Oshima and Shutaro Hori and Yutaka Nakano and Kazufumi Honda and Ayumi Kashiro and Chigusa Morizane and Satoshi Nara and Shojiro Kikuchi and Takahiko Shibahara and Makoto Itonaga and Masayuki Ono and Naoko Minegishi and Seizo Koshiba and Masayuki Yamamoto and Atsushi Kuno and Hiroshi Handa and Michiie Sakamoto and Makoto Suematsu and Yuko Kitagawa",

note = "Funding Information: Funding: This research was supported by AMED-CREST and AMED-Tailor-made Medical Treatment Program (to Y.K., Grant No: JP17gm0710010 and grant No.: JP17ek0109166)), JSPS KAKENHI (to Y.K., Grant No: 18K06921 and to Y.N., Grant No: 19K18132). This study was supported by grants from the Project for Cancer Research and Therapeutic Evolution (PCREATE) from AMED (20cm0106403h0005, KH). Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2020",

month = sep,

doi = "10.3390/cancers12092469",

language = "English",

volume = "12",

pages = "1--17",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "9",

}

Yokose, T, Kabe, Y, Matsuda, A, Kitago, M, Matsuda, S, Hirai, M, Nakagawa, T, Masugi, Y, Hishiki, T, Nakamura, Y, Shinoda, M, Yagi, H, Abe, Y, Oshima, G, Hori, S, Nakano, Y, Honda, K, Kashiro, A, Morizane, C, Nara, S, Kikuchi, S, Shibahara, T, Itonaga, M, Ono, M, Minegishi, N, Koshiba, S , Yamamoto, M, Kuno, A, Handa, H, Sakamoto, M, Suematsu, M & Kitagawa, Y 2020, 'O-glycan-altered extracellular vesicles: A specific serum marker elevated in pancreatic cancer', Cancers, vol. 12, no. 9, 2469, pp. 1-17. https://doi.org/10.3390/cancers12092469

TY - JOUR

T1 - O-glycan-altered extracellular vesicles

T2 - A specific serum marker elevated in pancreatic cancer

AU - Yokose, Takahiro

AU - Kabe, Yasuaki

AU - Matsuda, Atsushi

AU - Kitago, Minoru

AU - Matsuda, Sachiko

AU - Hirai, Miwa

AU - Nakagawa, Tomomi

AU - Masugi, Yohei

AU - Hishiki, Takako

AU - Nakamura, Yuki

AU - Shinoda, Masahiro

AU - Yagi, Hiroshi

AU - Abe, Yuta

AU - Oshima, Go

AU - Hori, Shutaro

AU - Nakano, Yutaka

AU - Honda, Kazufumi

AU - Kashiro, Ayumi

AU - Morizane, Chigusa

AU - Nara, Satoshi

AU - Kikuchi, Shojiro

AU - Shibahara, Takahiko

AU - Itonaga, Makoto

AU - Ono, Masayuki

AU - Minegishi, Naoko

AU - Koshiba, Seizo

AU - Yamamoto, Masayuki

AU - Kuno, Atsushi

AU - Handa, Hiroshi

AU - Sakamoto, Michiie

AU - Suematsu, Makoto

AU - Kitagawa, Yuko

N1 - Funding Information: Funding: This research was supported by AMED-CREST and AMED-Tailor-made Medical Treatment Program (to Y.K., Grant No: JP17gm0710010 and grant No.: JP17ek0109166)), JSPS KAKENHI (to Y.K., Grant No: 18K06921 and to Y.N., Grant No: 19K18132). This study was supported by grants from the Project for Cancer Research and Therapeutic Evolution (PCREATE) from AMED (20cm0106403h0005, KH). Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2020/9

Y1 - 2020/9

N2 - 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 by O-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 with O-glycans recognized by ABA/ACA are elevated in PC sera and can act as potential biomarkers in a liquid biopsy for PC patients screening.

AB - 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 by O-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 with O-glycans recognized by ABA/ACA are elevated in PC sera and can act as potential biomarkers in a liquid biopsy for PC patients screening.

KW - Extracellular vesicles

KW - Glycomics

KW - Lectin microarray

KW - Liquid biopsy

KW - O-glycan

KW - Pancreatic cancer

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UR - http://www.scopus.com/inward/citedby.url?scp=85090520975&partnerID=8YFLogxK

U2 - 10.3390/cancers12092469

DO - 10.3390/cancers12092469

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AN - SCOPUS:85090520975

SN - 2072-6694

VL - 12

SP - 1

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JO - Cancers

JF - Cancers

IS - 9

M1 - 2469

ER -

O-glycan-altered extracellular vesicles: A specific serum marker elevated in pancreatic cancer

Abstract

Keywords

UN SDGs

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