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A novel liver metastasis-correlated protein of pancreatic neuroendocrine neoplasm (PanNEN) discovered by proteomic analysis

The aim of this study was to identify novel liver metastasis-correlated proteins of PanNEN by proteomics to compare pancreatic tumor (PT) with paired metastatic liver tumor (LT). Of 118 surgical cases with PanNEN, 7 cases with formalin-fixed paraffin-embedded (FFPE) tissues of both PT and paired LT...

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Autores principales: Shimura, Mitsuhiro, Mizuma, Masamichi, Takadate, Tatsuyuki, Katoh, Yasutake, Suzuki, Takashi, Iseki, Masahiro, Hata, Tatsuo, Aoki, Shuichi, Suzuki, Yukie, Sakata, Naoaki, Ohtsuka, Hideo, Hayashi, Hiroki, Morikawa, Takanori, Nakagawa, Kei, Motoi, Fuyuhiko, Naitoh, Takeshi, Igarashi, Kazuhiko, Sasano, Hironobu, Unno, Michiaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966250/
https://www.ncbi.nlm.nih.gov/pubmed/29849941
http://dx.doi.org/10.18632/oncotarget.25110
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author Shimura, Mitsuhiro
Mizuma, Masamichi
Takadate, Tatsuyuki
Katoh, Yasutake
Suzuki, Takashi
Iseki, Masahiro
Hata, Tatsuo
Aoki, Shuichi
Suzuki, Yukie
Sakata, Naoaki
Ohtsuka, Hideo
Hayashi, Hiroki
Morikawa, Takanori
Nakagawa, Kei
Motoi, Fuyuhiko
Naitoh, Takeshi
Igarashi, Kazuhiko
Sasano, Hironobu
Unno, Michiaki
author_facet Shimura, Mitsuhiro
Mizuma, Masamichi
Takadate, Tatsuyuki
Katoh, Yasutake
Suzuki, Takashi
Iseki, Masahiro
Hata, Tatsuo
Aoki, Shuichi
Suzuki, Yukie
Sakata, Naoaki
Ohtsuka, Hideo
Hayashi, Hiroki
Morikawa, Takanori
Nakagawa, Kei
Motoi, Fuyuhiko
Naitoh, Takeshi
Igarashi, Kazuhiko
Sasano, Hironobu
Unno, Michiaki
author_sort Shimura, Mitsuhiro
collection PubMed
description The aim of this study was to identify novel liver metastasis-correlated proteins of PanNEN by proteomics to compare pancreatic tumor (PT) with paired metastatic liver tumor (LT). Of 118 surgical cases with PanNEN, 7 cases with formalin-fixed paraffin-embedded (FFPE) tissues of both PT and paired LT were evaluated by proteomics. Tumor cells were selectively collected from FFPE tissues by laser capture microdissection. A total of 3,722 proteins were detected from extracted peptides by mass spectrometry-based shotgun analysis. Selection of the candidate proteins expressed differently between PT and LT were performed by semi-quantitative comparison in silico and confirmation with immunohistochemistry. We focused on ANXA6, CNPY2, RAB11B and TUBB3, all of which had higher expressions in LT. In all surgical cases with FFPE samples, liver recurrence-free survival (RFS) was evaluated in correlation to the expression of the candidate proteins in PT by immunohistochemistry. Liver RFS was significantly poorer in CNPY2 positive patients than in negative patients (10-year liver RFS; 39.8% vs. 92.3%, p = 0.012). Also, liver RFS tended to be poorer in ANXA6 positive patients than in those who were negative (10-year liver RFS; 51.4% vs. 95.0%, p = 0.099). In the multivariate analysis, the independent predictors of liver RFS were CNPY2 positivity (HR: 6.19, 95 % CI: 1.47–42.79, p = 0.011) and tumor size ≥ 42 mm (HR: 4.63, 95 % CI: 1.03–23.23, p = 0.045). In conclusion, CNPY2 is a novel liver metastasis-correlated protein of PanNEN.
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spelling pubmed-59662502018-05-30 A novel liver metastasis-correlated protein of pancreatic neuroendocrine neoplasm (PanNEN) discovered by proteomic analysis Shimura, Mitsuhiro Mizuma, Masamichi Takadate, Tatsuyuki Katoh, Yasutake Suzuki, Takashi Iseki, Masahiro Hata, Tatsuo Aoki, Shuichi Suzuki, Yukie Sakata, Naoaki Ohtsuka, Hideo Hayashi, Hiroki Morikawa, Takanori Nakagawa, Kei Motoi, Fuyuhiko Naitoh, Takeshi Igarashi, Kazuhiko Sasano, Hironobu Unno, Michiaki Oncotarget Research Paper The aim of this study was to identify novel liver metastasis-correlated proteins of PanNEN by proteomics to compare pancreatic tumor (PT) with paired metastatic liver tumor (LT). Of 118 surgical cases with PanNEN, 7 cases with formalin-fixed paraffin-embedded (FFPE) tissues of both PT and paired LT were evaluated by proteomics. Tumor cells were selectively collected from FFPE tissues by laser capture microdissection. A total of 3,722 proteins were detected from extracted peptides by mass spectrometry-based shotgun analysis. Selection of the candidate proteins expressed differently between PT and LT were performed by semi-quantitative comparison in silico and confirmation with immunohistochemistry. We focused on ANXA6, CNPY2, RAB11B and TUBB3, all of which had higher expressions in LT. In all surgical cases with FFPE samples, liver recurrence-free survival (RFS) was evaluated in correlation to the expression of the candidate proteins in PT by immunohistochemistry. Liver RFS was significantly poorer in CNPY2 positive patients than in negative patients (10-year liver RFS; 39.8% vs. 92.3%, p = 0.012). Also, liver RFS tended to be poorer in ANXA6 positive patients than in those who were negative (10-year liver RFS; 51.4% vs. 95.0%, p = 0.099). In the multivariate analysis, the independent predictors of liver RFS were CNPY2 positivity (HR: 6.19, 95 % CI: 1.47–42.79, p = 0.011) and tumor size ≥ 42 mm (HR: 4.63, 95 % CI: 1.03–23.23, p = 0.045). In conclusion, CNPY2 is a novel liver metastasis-correlated protein of PanNEN. Impact Journals LLC 2018-05-11 /pmc/articles/PMC5966250/ /pubmed/29849941 http://dx.doi.org/10.18632/oncotarget.25110 Text en Copyright: © 2018 Shimura et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Shimura, Mitsuhiro
Mizuma, Masamichi
Takadate, Tatsuyuki
Katoh, Yasutake
Suzuki, Takashi
Iseki, Masahiro
Hata, Tatsuo
Aoki, Shuichi
Suzuki, Yukie
Sakata, Naoaki
Ohtsuka, Hideo
Hayashi, Hiroki
Morikawa, Takanori
Nakagawa, Kei
Motoi, Fuyuhiko
Naitoh, Takeshi
Igarashi, Kazuhiko
Sasano, Hironobu
Unno, Michiaki
A novel liver metastasis-correlated protein of pancreatic neuroendocrine neoplasm (PanNEN) discovered by proteomic analysis
title A novel liver metastasis-correlated protein of pancreatic neuroendocrine neoplasm (PanNEN) discovered by proteomic analysis
title_full A novel liver metastasis-correlated protein of pancreatic neuroendocrine neoplasm (PanNEN) discovered by proteomic analysis
title_fullStr A novel liver metastasis-correlated protein of pancreatic neuroendocrine neoplasm (PanNEN) discovered by proteomic analysis
title_full_unstemmed A novel liver metastasis-correlated protein of pancreatic neuroendocrine neoplasm (PanNEN) discovered by proteomic analysis
title_short A novel liver metastasis-correlated protein of pancreatic neuroendocrine neoplasm (PanNEN) discovered by proteomic analysis
title_sort novel liver metastasis-correlated protein of pancreatic neuroendocrine neoplasm (pannen) discovered by proteomic analysis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966250/
https://www.ncbi.nlm.nih.gov/pubmed/29849941
http://dx.doi.org/10.18632/oncotarget.25110
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