Prognostic relevance of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors

Abstract Prognostic biomarkers for the pancreatic neuroendocrine tumors are needed. Proteomic study on insulinoma has been rarely reported. We identified the differential expression of proteins between insulinoma and their paired tissues by proteomic analysis, and evaluated the prognostic significan...

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Autores principales: Yu-Li Song, Run Yu, Xin-Wei Qiao, Chun-Mei Bai, Chong-Mei Lu, Yu Xiao, Ding-Rong Zhong, Jie Chen, Yu-Pei Zhao, Tai-Ping Zhang, Tian-Tian Song, He-Li Gao, Ying-Hua Wan, Lin Shen, Bin Lv, Jian-Jiang Hao, Ye Zhang, Laura Tang, Yuan-Jia Chen
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:cdd41ba6f50b48ae95d0ff5540b121b42021-12-02T12:31:58ZPrognostic relevance of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors10.1038/s41598-017-02051-12045-2322https://doaj.org/article/cdd41ba6f50b48ae95d0ff5540b121b42017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02051-1https://doaj.org/toc/2045-2322Abstract Prognostic biomarkers for the pancreatic neuroendocrine tumors are needed. Proteomic study on insulinoma has been rarely reported. We identified the differential expression of proteins between insulinoma and their paired tissues by proteomic analysis, and evaluated the prognostic significance of specific proteins in pancreatic neuroendocrine tumors including insulinoma. The differential expression of select proteins was validated in more than 300 tumors using immunohistochemical staining and western blot. Methylation of UCH-L1 promoter in tumors was examined by methylation specific PCR and validated by sequencing. The concurrent expression of UCH-L1 and α-internexin was correlated with the prognosis in 2 independent collectives of patients with tumors. Sixty-two and 219 proteins were significantly down-regulated and up-regulated in insulinomas, respectively. Demethylation of UCH-L1 promoter was associated with UCH-L1 expression in tumors (p = 0.002). The concurrent expression of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors was significantly associated with better overall survival and disease-free survival in the combination of both cohorts (log rank p = 3.90 × 10−4 and p = 3.75 × 10−5, respectively) and in each of cohorts. The prognostic value of both proteins was also validated in patients with stage II and III tumors (p = 0.017 and p = 0.006, respectively). The proteins UCH-L1 and α-internexin could be independent prognostic biomarkers of pancreatic neuroendocrine tumors.Yu-Li SongRun YuXin-Wei QiaoChun-Mei BaiChong-Mei LuYu XiaoDing-Rong ZhongJie ChenYu-Pei ZhaoTai-Ping ZhangTian-Tian SongHe-Li GaoYing-Hua WanLin ShenJie ChenBin LvJian-Jiang HaoYe ZhangLaura TangYuan-Jia ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yu-Li Song
Run Yu
Xin-Wei Qiao
Chun-Mei Bai
Chong-Mei Lu
Yu Xiao
Ding-Rong Zhong
Jie Chen
Yu-Pei Zhao
Tai-Ping Zhang
Tian-Tian Song
He-Li Gao
Ying-Hua Wan
Lin Shen
Jie Chen
Bin Lv
Jian-Jiang Hao
Ye Zhang
Laura Tang
Yuan-Jia Chen
Prognostic relevance of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors
description Abstract Prognostic biomarkers for the pancreatic neuroendocrine tumors are needed. Proteomic study on insulinoma has been rarely reported. We identified the differential expression of proteins between insulinoma and their paired tissues by proteomic analysis, and evaluated the prognostic significance of specific proteins in pancreatic neuroendocrine tumors including insulinoma. The differential expression of select proteins was validated in more than 300 tumors using immunohistochemical staining and western blot. Methylation of UCH-L1 promoter in tumors was examined by methylation specific PCR and validated by sequencing. The concurrent expression of UCH-L1 and α-internexin was correlated with the prognosis in 2 independent collectives of patients with tumors. Sixty-two and 219 proteins were significantly down-regulated and up-regulated in insulinomas, respectively. Demethylation of UCH-L1 promoter was associated with UCH-L1 expression in tumors (p = 0.002). The concurrent expression of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors was significantly associated with better overall survival and disease-free survival in the combination of both cohorts (log rank p = 3.90 × 10−4 and p = 3.75 × 10−5, respectively) and in each of cohorts. The prognostic value of both proteins was also validated in patients with stage II and III tumors (p = 0.017 and p = 0.006, respectively). The proteins UCH-L1 and α-internexin could be independent prognostic biomarkers of pancreatic neuroendocrine tumors.
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author Yu-Li Song
Run Yu
Xin-Wei Qiao
Chun-Mei Bai
Chong-Mei Lu
Yu Xiao
Ding-Rong Zhong
Jie Chen
Yu-Pei Zhao
Tai-Ping Zhang
Tian-Tian Song
He-Li Gao
Ying-Hua Wan
Lin Shen
Jie Chen
Bin Lv
Jian-Jiang Hao
Ye Zhang
Laura Tang
Yuan-Jia Chen
author_facet Yu-Li Song
Run Yu
Xin-Wei Qiao
Chun-Mei Bai
Chong-Mei Lu
Yu Xiao
Ding-Rong Zhong
Jie Chen
Yu-Pei Zhao
Tai-Ping Zhang
Tian-Tian Song
He-Li Gao
Ying-Hua Wan
Lin Shen
Jie Chen
Bin Lv
Jian-Jiang Hao
Ye Zhang
Laura Tang
Yuan-Jia Chen
author_sort Yu-Li Song
title Prognostic relevance of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors
title_short Prognostic relevance of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors
title_full Prognostic relevance of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors
title_fullStr Prognostic relevance of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors
title_full_unstemmed Prognostic relevance of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors
title_sort prognostic relevance of uch-l1 and α-internexin in pancreatic neuroendocrine tumors
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/cdd41ba6f50b48ae95d0ff5540b121b4
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