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
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) cel...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007017/ |
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pubmed-5007017 |
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pubmed-50070172016-09-27 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 Yoneyama, Toshihiro Ohtsuki, Sumio Honda, Kazufumi Kobayashi, Makoto Iwasaki, Motoki Uchida, Yasuo Okusaka, Takuji Nakamori, Shoji Shimahara, Masashi Ueno, Takaaki Tsuchida, Akihiko Sata, Naohiro Ioka, Tatsuya Yasunami, Yohichi Kosuge, Tomoo Kaneda, Takashi Kato, Takao Yagihara, Kazuhiro Fujita, Shigeyuki Huang, Wilber Yamada, Tesshi Tachikawa, Masanori Terasaki, Tetsuya Research Article 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. Public Library of Science 2016-08-31 /pmc/articles/PMC5007017/ /pubmed/27579675 http://dx.doi.org/10.1371/journal.pone.0161009 Text en © 2016 Yoneyama et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Yoneyama, Toshihiro Ohtsuki, Sumio Honda, Kazufumi Kobayashi, Makoto Iwasaki, Motoki Uchida, Yasuo Okusaka, Takuji Nakamori, Shoji Shimahara, Masashi Ueno, Takaaki Tsuchida, Akihiko Sata, Naohiro Ioka, Tatsuya Yasunami, Yohichi Kosuge, Tomoo Kaneda, Takashi Kato, Takao Yagihara, Kazuhiro Fujita, Shigeyuki Huang, Wilber Yamada, Tesshi Tachikawa, Masanori Terasaki, Tetsuya |
| spellingShingle |
Yoneyama, Toshihiro Ohtsuki, Sumio Honda, Kazufumi Kobayashi, Makoto Iwasaki, Motoki Uchida, Yasuo Okusaka, Takuji Nakamori, Shoji Shimahara, Masashi Ueno, Takaaki Tsuchida, Akihiko Sata, Naohiro Ioka, Tatsuya Yasunami, Yohichi Kosuge, Tomoo Kaneda, Takashi Kato, Takao Yagihara, Kazuhiro Fujita, Shigeyuki Huang, Wilber Yamada, Tesshi Tachikawa, Masanori Terasaki, Tetsuya 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 |
| author_facet |
Yoneyama, Toshihiro Ohtsuki, Sumio Honda, Kazufumi Kobayashi, Makoto Iwasaki, Motoki Uchida, Yasuo Okusaka, Takuji Nakamori, Shoji Shimahara, Masashi Ueno, Takaaki Tsuchida, Akihiko Sata, Naohiro Ioka, Tatsuya Yasunami, Yohichi Kosuge, Tomoo Kaneda, Takashi Kato, Takao Yagihara, Kazuhiro Fujita, Shigeyuki Huang, Wilber Yamada, Tesshi Tachikawa, Masanori Terasaki, Tetsuya |
| author_sort |
Yoneyama, Toshihiro |
| title |
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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| description |
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. |
| publisher |
Public Library of Science |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007017/ |
| _version_ |
1613640484338532352 |