HMGB1 correlates with angiogenesis and poor prognosis of perihilar cholangiocarcinoma via elevating VEGFR2 of vessel endothelium

Perihilar cholangiocarcinoma (PHCCA) is the most common type of cholangiocarcinoma with low resection rate and high morbidity. The study of PHCCA biomarkers made progresses slowly compared with intrahepatic cholangiocarcinoma because of surgical complexity and low possibility of radical surgery, whi...

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Vydáno v:Oncogene Ročník 38; číslo 6; s. 868 - 880
Hlavní autoři: Xu, Yun-Fei, Liu, Zeng-Li, Pan, Chang, Yang, Xiao-Qing, Ning, Shang-Lei, Liu, Hong-Da, Guo, Sen, Yu, Jin-Ming, Zhang, Zong-Li
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 01.02.2019
Nature Publishing Group
Témata:
631/67
692/53/2422
Angiogenesis
Apoptosis
Bile
Bile Duct Neoplasms - blood
Bile Duct Neoplasms - mortality
Bile Duct Neoplasms - surgery
Bile ducts
Biliary tract cancer
Biological markers
Biomarkers
Cancer therapies
Care and treatment
Cell Biology
Cholangiocarcinoma
Cholangitis
Chromosomal proteins
Clinical significance
Development and progression
Disease-Free Survival
Endothelial cells
Endothelial Cells - metabolism
Endothelial Cells - pathology
Endothelium
Epidermal growth factor receptors
Female
Gene expression
Genetic aspects
Health aspects
HMGB1 protein
HMGB1 Protein - blood
Human Genetics
Humans
Immune response
Immunohistochemistry
Internal Medicine
Intracellular
Klatskin Tumor - blood
Klatskin Tumor - mortality
Klatskin Tumor - surgery
Lipopolysaccharides
Male
Medical prognosis
Medicine
Medicine & Public Health
Metastasis
Microvasculature
Morbidity
Multivariate analysis
Neoplasm Proteins - blood
Neovascularization, Pathologic - blood
Neovascularization, Pathologic - mortality
Neovascularization, Pathologic - surgery
Oncology
Patients
Prognosis
Prospective Studies
Surgery
Survival Rate
Transcription factors
Vascular endothelial growth factor
ISSN:0950-9232, 1476-5594, 1476-5594
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Shrnutí:Perihilar cholangiocarcinoma (PHCCA) is the most common type of cholangiocarcinoma with low resection rate and high morbidity. The study of PHCCA biomarkers made progresses slowly compared with intrahepatic cholangiocarcinoma because of surgical complexity and low possibility of radical surgery, which resulted in the difficulty of specimen obtainment. To screen and identify new biomarkers in PHCCA, we constructed a retrospective cohort with 121 PHCCA patients and a prospective cohort consisting of 64 PHCCA patients, and screened the candidate biomarkers by immunohistochemistry and quantified PCR. In our study, expression of high mobility group box 1 (HMGB1) was demonstrated to be significantly associated with microvascular density (MVD) and unfavorable prognosis of PHCCA in both retrospective and prospective study. Moreover, HMGB1 concentrations in bile and serum of PHCCA patients and healthy controls were detected and compared. Postoperative serum HMGB1 and reflux cholangitis indicated recurrence and unfavorable prognosis of PHCCA. With experiments in vitro and in vivo, we demonstrated that intracellular HMGB1 could be released from PHCCA cells and induce invasion and angiogenesis with LPS stimulation. VEGFR2 expression in vessel endothelial cells was upregulated by the released HMGB1 from PHCCA, resulting in the ectopic angiogenesis. In conclusion, intracellular HMGB1 could be released from PHCCA cells and promote angiogenesis via elevating VEGFR2 in vessel endothelial cells. High expression of HMGB1 was associated with MVD and poor prognosis in clinical analyzation. Postoperative serum HMGB1 and cholangitis could predict high recurrence and unfavorable prognosis.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0950-9232
1476-5594
1476-5594
DOI:10.1038/s41388-018-0485-8