TY - JOUR
T1 - 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
AU - Yoneyama, Toshihiro
AU - Ohtsuki, Sumio
AU - Honda, Kazufumi
AU - Kobayashi, Makoto
AU - Iwasaki, Motoki
AU - Uchida, Yasuo
AU - Okusaka, Takuji
AU - Nakamori, Shoji
AU - Shimahara, Masashi
AU - Ueno, Takaaki
AU - Tsuchida, Akihiko
AU - Sata, Naohiro
AU - Ioka, Tatsuya
AU - Yasunami, Yohichi
AU - Kosuge, Tomoo
AU - Kaneda, Takashi
AU - Kato, Takao
AU - Yagihara, Kazuhiro
AU - Fujita, Shigeyuki
AU - Huang, Wilber
AU - Yamada, Tesshi
AU - Tachikawa, Masanori
AU - Terasaki, Tetsuya
N1 - Funding Information:
This study was performed as a research program in the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct, 14089014), Ministry of Education, Culture, Sports, Science and Technology of Japan (http://www.mext.go.jp).This study was also supported in part by JSPS KAKENHI Grant Numbers 14J05219
Publisher Copyright:
© 2016 Yoneyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/8
Y1 - 2016/8
N2 - 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 IDACPV 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.
AB - 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 IDACPV 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.
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U2 - 10.1371/journal.pone.0161009
DO - 10.1371/journal.pone.0161009
M3 - Article
C2 - 27579675
AN - SCOPUS:84992390784
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 8
M1 - e0161009
ER -