Progranulin as a predictive factor of response to chemotherapy in advanced biliary tract carcinoma

• DOI: 10.1007/s00280-016-3170-z
• Publication Date: 2016-10-15T11:23:37Z
• Authors: Jong-Ho Kim; In-Gu Do; Kyungeun Kim; Jin Hee Sohn; Hong Joo Kim; Woo Kyu Jeon; Sung Ryol Lee; Byung Ho Son; Jun Ho Shin; Heerim Nam; Heon-Ju Kwon; Mi Sung Kim; Hyun Pyo Hong; Ginette Serrero; Dong-Hoe Koo
• Keywords: Adult; Male; 0301 basic medicine; Palliative Care; Middle Aged; Prognosis; Disease-Free Survival; 3. Good health; 03 medical and health sciences; Biliary Tract Neoplasms; Progranulins; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; Humans; Intercellular Signaling Peptides and Proteins; Female; Biomarkers; Aged; Follow-Up Studies; Retrospective Studies

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).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.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).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.