title: Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker.
abstract: Cholangiocarcinoma (CCA) is a devastating disease due to resistance to traditional chemotherapies and radiotherapies. New therapeutic strategies against CCA are urgently needed. This study investigated the role of lipocalin-2 (LCN2) in human cholangiocarcinoma as a potential therapeutic target and diagnostic marker. So far, the role of LCN2 in cancer is still controversial and studies regarding the role of LCN2 in CCA are limited. LCN2 knockdown inhibited CCA cell growth in vitro and in vivo through induction of cell cycle arrest at G0/G1 phases and decreased metastatic potential due to repression of epithelial-mesenchymal transition (EMT). Overexpression of LCN2 in CCA cells increased cell metastatic potential. We showed for the first time that the N-myc downstream regulated gene 1 (NDRG1) and NDRG2, known as tumor suppressor genes, are negatively regulated by LCN2 in CCA cells. LCN2 concentration in bile was higher in patients with CCA than that in patients with gallstones, with a cutoff value of 20.08 ng/ml making this a potential diagnostic marker. Higher LCN2 expression was associated with worse survival in patients with CCA. LCN2 is a promising target for CCA treatment and bile LCN2 level is a potential diagnostic marker for CCA.
authors: General Surgery Department, Chang Gung Memorial Hospital, Chang Gung University, Keelung, Taiwan, R.O.C.|Director of Zebrafish center of Keelung Chang Gung Memorial Hospital, Taiwan, R.O.C.
authors: Kun-Chun
authors: KC
authors: Chiang
authors: General Surgery Department and Liver research center, Chang Gung Memorial Hospital, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan, R.O.C.
authors: Ta-Sen
authors: TS
authors: Yeh
authors: Department of Pathology and Liver research center, Chang Gung Memorial Hospital, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan, R.O.C.
authors: Ren-Chin
authors: RC
authors: Wu
authors: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan, R.O.C.
authors: Jong-Hwei S
authors: JS
authors: Pang
authors: General Surgery Department and Liver research center, Chang Gung Memorial Hospital, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan, R.O.C.
authors: Chi-Tung
authors: CT
authors: Cheng
authors: General Surgery Department and Liver research center, Chang Gung Memorial Hospital, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan, R.O.C.
authors: Shang-Yu
authors: SY
authors: Wang
authors: Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan Taoyuan, Taiwan, 333, R.O.C.|Department of Urology, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan, ROC.
authors: Horng-Heng
authors: HH
authors: Juang
authors: General Surgery Department and Liver research center, Chang Gung Memorial Hospital, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan, R.O.C.
authors: Chun-Nan
authors: CN
authors: Yeh
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D058750:Epithelial-Mesenchymal Transition; D059585:G1 Phase Cell Cycle Checkpoints; D042882:Gallstones / Q000378:metabolism / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000071068:Lipocalin-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000071068:Lipocalin-2; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C466228:NDRG2 protein, human