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Overexpression of 14-3-3δ Predicts Poor Prognosis in Extrahepatic Cholangiocarcinoma Patients

The protein 14-3-3δ interacts with Trp53 to maintain G2 arrest and thus regulates the cell cycle. Though dysfunction of 14-3-3δ caused by hyper-methylation of CpG islands was reported in several carcinomas, the exact role of this protein in the development of extrahepatic cholangiocarcinoma has not...

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Published in:BioMed research international 2020, Vol.2020 (2020), p.1-6
Main Authors: He, Qiang, Zhang, Xingmao, Li, Xianliang, Lang, Ren, Fan, Hua, Wu, Qiao, Lv, Shaocheng
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description The protein 14-3-3δ interacts with Trp53 to maintain G2 arrest and thus regulates the cell cycle. Though dysfunction of 14-3-3δ caused by hyper-methylation of CpG islands was reported in several carcinomas, the exact role of this protein in the development of extrahepatic cholangiocarcinoma has not been fully elucidated. Here, we aim at investigating the clinical relevance between 14-3-3δ and human extrahepatic cholangiocarcinoma. We collected extrahepatic cholangiocarcinoma specimens of 65 patients in Beijing Chao Yang Hospital and evaluated their 14-3-3δ expression using immunohistochemistry. We categorized the patients into different subgroups according to clinic pathological factors, such as sex, age, tumor size, pathological classification, lymph node metastasis status, tumor stage, and serum markers including CEA, CA-242, or CA19-9, and further evaluated the correlation between 14-3-3δ expression and these potential prognostic factors. As a result, we detected 14-3-3δ expression in 53 out of 65 specimens (81.5%), and the expression was positively correlated with TNM stage, lymph node metastasis, and overall survival. Our results suggest that 14-3-3δ serves as an oncogenic driver in extrahepatic cholangiocarcinoma tumorigenesis rather than a cell cycle regulator; the overexpression of 14-3-3δ might be frequently acquired by tumor cells to escape appropriate cell cycle regulation. Thus, 14-3-3δ could be a potential target for extrahepatic cholangiocarcinoma diagnosis and therapy.
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Though dysfunction of 14-3-3δ caused by hyper-methylation of CpG islands was reported in several carcinomas, the exact role of this protein in the development of extrahepatic cholangiocarcinoma has not been fully elucidated. Here, we aim at investigating the clinical relevance between 14-3-3δ and human extrahepatic cholangiocarcinoma. We collected extrahepatic cholangiocarcinoma specimens of 65 patients in Beijing Chao Yang Hospital and evaluated their 14-3-3δ expression using immunohistochemistry. We categorized the patients into different subgroups according to clinic pathological factors, such as sex, age, tumor size, pathological classification, lymph node metastasis status, tumor stage, and serum markers including CEA, CA-242, or CA19-9, and further evaluated the correlation between 14-3-3δ expression and these potential prognostic factors. As a result, we detected 14-3-3δ expression in 53 out of 65 specimens (81.5%), and the expression was positively correlated with TNM stage, lymph node metastasis, and overall survival. Our results suggest that 14-3-3δ serves as an oncogenic driver in extrahepatic cholangiocarcinoma tumorigenesis rather than a cell cycle regulator; the overexpression of 14-3-3δ might be frequently acquired by tumor cells to escape appropriate cell cycle regulation. 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This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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subjects 14-3-3 Proteins - biosynthesis
14-3-3 Proteins - metabolism
Aged
Antibodies
Apoptosis
Bile Duct Neoplasms - diagnosis
Bile Duct Neoplasms - metabolism
Bile Duct Neoplasms - pathology
Biomarkers, Tumor - metabolism
Cancer therapies
Carcinoma
Cell cycle
Cholangiocarcinoma
Cholangiocarcinoma - diagnosis
Cholangiocarcinoma - metabolism
Cholangiocarcinoma - pathology
CpG islands
DNA methylation
Evaluation
Female
Gender
Humans
Immunohistochemistry
Lymph nodes
Lymphatic Metastasis
Lymphatic system
Male
Medical prognosis
Metastases
Metastasis
Middle Aged
Neoplasm Staging
Patients
Proteins
Subgroups
Survival Rate
Tumor cells
Tumorigenesis
Tumors
title Overexpression of 14-3-3δ Predicts Poor Prognosis in Extrahepatic Cholangiocarcinoma Patients
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