title: Beclin 1 deficiency correlated with lymph node metastasis, predicts a distinct outcome in intrahepatic and extrahepatic cholangiocarcinoma.
abstract: Autophagy can be tumor suppressive as well as promotive in regulation of tumorigenesis and disease progression. Accordingly, the prognostic significance of autophagy key regulator Beclin 1 was varied among different tumors. Here, we detected the clinicopathological and prognostic effect of Beclin 1 in the subtypes of intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). Beclin 1 expression level was detected by immunohistochemistry staining in 106 ICC and 74 ECC patients. We found that Beclin 1 was lowly expressed in 126 (70%) cholangiocarcinoma patients, consist of 72 ICC and 54 ECC. Moreover, the cholangiocarcinoma patients with lymph node metastasis (N1) had a lower Beclin 1 level than that of N0 subgroup (P=0.012). However, we did not detect any correlations between Beclin 1 and other clinicopathological features, including tumor subtypes, vascular invasion, HBV infection, liver cirrhosis, cholecystolithiasis and TNM stage. Survival analysis showed that, compared with the high expression subset, Beclin 1 low expression was correlated with a poorer 3-year progression-free survival (PFS, 69.1% VS 46.8%, P=041) for cholangiocarcinoma. Importantly, our stratified univariate and multivariate analysis confirmed that Beclin 1 lowly expressed ICC had an inferior PFS as well as overall survival than ECC, particularly than that of Beclin 1 highly expressed ECC patients. Thus, our study demonstrated that Beclin 1low expression, correlated with lymph node metastasis, and might be a negative prognostic biomarker for cholangiocarcinoma. Combined Beclin 1 level with the anatomical location might lead to refined prognosis for the subtypes of ICC and ECC.
authors.affiliation: Department of Medical Oncology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Wang
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Cao
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Xia
authors.forename: Xin-Juan
authors.initials: XJ
authors.lastname: Fan
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Ma
authors.forename: Qu
authors.initials: Q
authors.lastname: Lin
authors.forename: Chang-Chang
authors.initials: CC
authors.lastname: Jia
authors.forename: Min
authors.initials: M
authors.lastname: Dong
authors.forename: Dan-Yun
authors.initials: DY
authors.lastname: Ruan
authors.forename: Ze-Xiao
authors.initials: ZX
authors.lastname: Lin
authors.forename: Jing-Yun
authors.initials: JY
authors.lastname: Wen
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Zhan-Hong
authors.initials: ZH
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Xiang-Yuan
authors.initials: XY
authors.lastname: Wu
authors.forename: Xiang-Bo
authors.initials: XB
authors.lastname: Wan
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000071186:Beclin-1; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D047368:Tumor Burden
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins