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Identification of MicroRNA-21 as a Biomarker for Chemoresistance and Clinical Outcome Following Adjuvant Therapy in Resectable Pancreatic Cancer

Cited 228 time in Web of Science Cited 259 time in Scopus
Authors
Hwang, Jin-Hyeok; Voortman, Johannes; Giovannetti, Elisa; Steinberg, Seth M.; Kim, Yong-Tae; Park, Joo Kyung; Kang, Gyeong Hoon; Del Chiaro, Marco; Giaccone, Giuseppe; Peters, Godefridus J.; Kim, Sun-Whe; Kim, Min A.; Funel, Niccola; Leon, Leticia G.
Issue Date
2010-05-14
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE; Vol.5 5; e10630
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The high risk of recurrence following surgical resection provides the rationale for adjuvant therapy. However, only a subset of patients benefit from adjuvant therapy. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of novel candidate biomarkers, including microRNAs, can predict clinical outcome in PDAC patients treated with adjuvant therapy. Methodology/Principal Findings: Formalin-fixed paraffin embedded specimens from a cohort of 82 resected Korean PDAC cases were analyzed for protein expression by immunohistochemistry and for microRNA expression using quantitative Real-Time PCR. Cox proportional hazards model analysis in the subgroup of patients treated with adjuvant therapy (N = 52) showed that lower than median miR-21 expression was associated with a significantly lower hazard ratio (HR) for death (HR = 0.316; 95% CI = 0.166-0.600; P = 0.0004) and recurrence (HR = 0.521; 95% CI = 0.280-0.967; P = 0.04). MiR-21 expression status emerged as the single most predictive biomarker for treatment outcome among all 27 biological and 9 clinicopathological factors evaluated. No significant association was detected in patients not treated with adjuvant therapy. In an independent validation cohort of 45 frozen PDAC tissues from Italian cases, all treated with adjuvant therapy, lower than median miR-21 expression was confirmed to be correlated with longer overall as well as disease-free survival. Furthermore, transfection with anti-miR-21 enhanced the chemosensitivity of PDAC cells. Conclusions Significance: Low miR-21 expression was associated with benefit from adjuvant treatment in two independent cohorts of PDAC cases, and anti-miR-21 increased anticancer drug activity in vitro. These data provide evidence that miR-21 may allow stratification for adjuvant therapy, and represents a new potential target for therapy in PDAC.
ISSN
1932-6203
Language
English
URI
https://hdl.handle.net/10371/76542
DOI
https://doi.org/10.1371/journal.pone.0010630
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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