title: Prognostic significance of Beclin 1 in intrahepatic cholangiocellular carcinoma.
abstract: Autophagy enables cells to recycle long-lived proteins or damaged organelles. Beclin 1 plays important roles in autophagy, differentiation, apoptosis and the development and progression of cancer, but the expression of Beclin 1 and its possible role in primary intrahepatic cholangiocarcinoma (ICC) has not been reported yet. This study aimed to investigate Beclin 1 expression and its prognostic significance in ICC. First, we assessed the expression levels of Becn1 by real-time PCR in 50 ICC samples and found Becn1 mRNA expression was markedly increased in 78% (39 of 50) samples compared with normal bile duct epithelium. Beclin 1 protein expression in 108 tumor specimens from patients diagnosed with ICC was examined by immunohistochemistry and the correlation between Beclin 1 expression and clinicopathological factors were investigated. Immunopositivity for Beclin 1 was found in 72.2% (78 of 108) samples and low Beclin 1 expression was significantly associated with lymph node metastasis. The correlation between Beclin 1 expression and metastasis was validated in 46 ICC samples with lymph node metastasis. In survival analysis, low Beclin 1 expression was associated with worse overall survival (OS; p = 0.025) and disease-free survival (DFS; p = 0.027). In multivariate analysis, Beclin 1 expression, intrahepatic metastasis, lymph node metastasis and tumor size were found to be independent prognostic factors of OS. Thus, our results suggested the expression of Beclin 1 was correlated with progression and metastasis of ICC and it might serve as a novel prognostic marker for patients with ICC.
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, the Second Military Medical University, Shanghai, China.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Dong
authors.forename: Yu-Jie Hou
authors.initials: YJ
authors.lastname: Hou
authors.forename: Ye-Xiong
authors.initials: YX
authors.lastname: Tan
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Pan
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D012333:RNA, Messenger