title: Notch1 contributes to chemoresistance to gemcitabine and serves as an unfavorable prognostic indicator in pancreatic cancer.
abstract: BACKGROUND
  Pancreatic cancer (PC) carries frequent chemoresistance and extremely dismal prognosis. The underlying mechanisms remain to be further elucidated. We here report the role of Notch1 in gemcitabine resistance and its prognostic significance in PC.
  
  
  METHODS
  A small interfering RNA (siRNA) specifically targeting Notch1 was transiently transfected into three PC cell lines (AsPC-1, BxPC-3, and MIA PaCa-2), followed by examination of chemosensitivity to gemcitabine. On the other hand, Notch1 expression was evaluated immunohistochemically and correlated with clinicopathological and prognostic variables.
  
  
  RESULTS
  Successful knockdown of Notch1 by specific siRNA induced increased chemosensitivity to gemcitabine in all three cell lines. Immunohistochemical staining revealed that Notch1 was highly expressed in PC tissues (54.8 %), in contrast to that in para-tumor tissues (16.4 %). In addition, Notch1 positivity was significantly correlated with early-term metastasis and shortened overall survival. Multivariate Cox regression identified Notch1 as an independent prognostic factor.
  
  
  CONCLUSIONS
  Notch1 contributes to chemoresistance to gemcitabine, and serves as a significant indicator of unfavorable prognosis in PC.
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, National Laboratory of Medical Molecular Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Du
authors.forename: Yu-Pei
authors.initials: YP
authors.lastname: Zhao
authors.forename: Tai-Ping
authors.initials: TP
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Ge
authors.initials: G
authors.lastname: Chen
authors.forename: Quan-Cai
authors.initials: QC
authors.lastname: Cui
authors.forename: Jie
authors.initials: J
authors.lastname: Shi
authors.forename: Tian-Xiao
authors.initials: TX
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: You
authors.forename: Hong
authors.initials: H
authors.lastname: Shu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D003841:Deoxycytidine; D000093542:Gemcitabine