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Identification of microRNA-21 as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer.
- Source :
-
PloS one [PLoS One] 2010 May 14; Vol. 5 (5), pp. e10630. Date of Electronic Publication: 2010 May 14. - Publication Year :
- 2010
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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.<br />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.<br />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.
- Subjects :
- Aged
Biomarkers, Tumor metabolism
Carcinoma, Pancreatic Ductal drug therapy
Carcinoma, Pancreatic Ductal genetics
Carcinoma, Pancreatic Ductal pathology
Carcinoma, Pancreatic Ductal surgery
Cell Proliferation drug effects
Chemotherapy, Adjuvant
Cohort Studies
Disease-Free Survival
Drug Resistance, Neoplasm drug effects
Female
Fluorouracil pharmacology
Gene Expression Regulation, Neoplastic drug effects
Humans
Italy
Korea
Male
MicroRNAs metabolism
Middle Aged
Multivariate Analysis
Oligonucleotide Array Sequence Analysis
Pancreatic Neoplasms pathology
Pancreatic Neoplasms surgery
Proportional Hazards Models
Recurrence
Reproducibility of Results
Treatment Outcome
Biomarkers, Tumor genetics
Drug Resistance, Neoplasm genetics
MicroRNAs genetics
Pancreatic Neoplasms drug therapy
Pancreatic Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 5
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 20498843
- Full Text :
- https://doi.org/10.1371/journal.pone.0010630