title: Progranulin as a predictive factor of response to chemotherapy in advanced biliary tract carcinoma.
abstract: OBJECTIVE
  Progranulin (PGRN), characterized as an autocrine growth and survival factor, is known to stimulate the proliferation and survival of several cancer cell types. However, little is known about the prognostic role of PGRN in advanced biliary tract cancers (BTCs).
  
  
  METHODS
  A retrospective analysis was performed on patients with advanced BTC who received palliative chemotherapy between July 2004 and November 2014. PGRN expression was immunohistochemically evaluated according to staining intensity of tumor and peritumoral cells.
  
  
  RESULTS
  A total of 80 patients (39 intrahepatic, 26 extrahepatic, and 18 gallbladder tumors) were analyzed. The median age was 64 years (range 31-79), and 48 patients (60 %) were male. Thirty-five patients (44 %) had high tumor PGRN expression (PGRN positive), and there was a trend of poorer response to chemotherapy in patients with PGRN-positive tumor in terms of overall response rate (7 vs. 18 %). With a median follow-up duration of 17.7 months (range 4.9-35.1), PGRN-positive patients had worse progression-free survival (PFS) with a median of 2.7 months compared to 5.0 months for PGRN-negative patients (P = 0.023). After adjusting for possible confounding factors including sex, age, performance status, disease status, and chemotherapy agent, multivariate analysis showed that PGRN-positive tumor was a prognostic factor independently associated with poor PFS (hazard ratio 1.69, 95 % CI 1.02-2.81; P = 0.044).
  
  
  CONCLUSIONS
  PGRN overexpression was significantly associated with poor PFS in advanced BTCs. PGRN expression by IHC analysis might help predict treatment outcomes and provide a new target for molecular therapy.
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: In-Gu
authors.initials: IG
authors.lastname: Do
authors.affiliation: Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyungeun
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Sohn
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hong Joo
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Woo Kyu
authors.initials: WK
authors.lastname: Jeon
authors.affiliation: Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sung Ryol
authors.initials: SR
authors.lastname: Lee
authors.affiliation: Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Son
authors.affiliation: Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Radiation Oncology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Heerim
authors.initials: H
authors.lastname: Nam
authors.affiliation: Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Heon-Ju
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Mi Sung
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyun Pyo
authors.initials: HP
authors.lastname: Hong
authors.affiliation: A&G Pharmaceutical, Inc., Columbia, MD, USA.|Program in Oncology, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: Ginette
authors.initials: G
authors.lastname: Serrero
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Korea. d.h.koo@samsung.com.
authors.forename: Dong-Hoe
authors.initials: DH
authors.lastname: Koo
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000097:blood* / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D011379:Prognosis; D000077153:Progranulins; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins
keywords: Biliary tract cancer; Chemotherapy; Progranulin; Response