Journal List > Korean J Gastroenterol > v.66(4) > 1007429

Paik, Song, Kim, Kim, and Hwang: MicroRNA-200c as a Prognostic Biomarker for Pancreatic Cancer



MicroRNA (miRNA) regulates messenger RNA stability and translation. In cancer biology, miRNA affects the growth and metastasis of cancer cells by controlling epithelial-mesenchymal transition (EMT). MiR-200 family (200a/200b/ 200c/141) and miR-205 are associated with the regulation of EMT. We investigated the prognostic role of EMT-related miRNAs in pancreatic cancer.


We analyzed miR-200 family and miR-205 expression in tissue samples of 84 patients who underwent radical resection for pancreatic cancer.


Patients were followed from the date of diagnosis until death or censoring. The mean overall survival was 25.0±2.0 months (2–140 months). The R0 resection rate was obtained in 84.5% (n=71) of patients. The relative expressions of miR-200a/200b/200c/141 and miR-205 were 266.9±57.3/18.5±2.2/0.7±0.1/27.2±6.6 folds and 0.1±0.1 compared with human pancreatic ductal epithelial cells, respectively. Overall survival was longer in the low miR-200c expression group than in the high expression group (35 vs. 19 months, p=0.013). Multivariate analysis confirmed that patients with low miR-200c expression survived longer than the high expression group (hazard ratio, 1.771; 95% CI, 1.081–2.900; p=0.023). There was a trend toward longer disease-free survival in low miR-200c group without statistical significance (p=0.061).


The expression of miR-200c may be an important prognosis factor in pancreatic cancer, and it could be a novel therapeutic target of pancreatic cancer.


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Fig. 1.
Overall survival (p=0.013) (A) and disease-free survival (p=0.061) (B) according to the level of microRNA (miRNA)-200c.
Table 1.
The MicroRNA (miRNA) Primer Sequences for Quantitative Real-time PCR Analysis
miRNA Primer sequences
Table 2.
Baseline Characteristics of 84 Resected Pancreatic Cancer Patients
Characteristic Data
Age (yr) 64 (44–83)
Sex, male 52 (61.9)
Pathology, adenocarcinoma 79 (94.1)
R0 resection 71 (84.5)
pT stage  
 T1/T2 0 (0)/2 (2.4)
 T3/T4 81 (96.4)/1 (1.2)
pN stage  
 N0/N1 36 (42.9)/48 (57.1)
AJCC stage  
 IB 1 (1.2)
 IIA/IIB 37 (44.1)/45 (53.6)
 III 1 (1.2)
 Angiolymphatic 39 (46.4)
 Venous 17 (20.2)
 Perineural 59 (70.2)
Adjuvant chemotherapy 43 (51.2)
 Gemcitabine based 17 (20.2)
Adjuvant radiation therapy 45 (53.6)
Recurrence 70 (83.3)
 Local recurrence 25 (29.8)
 Distant metastasis 45 (53.6)

Values are presented as median (range) or n (%).

AJCC, American Joint Committee on Cancer.

Table 3.
MicroRNA (miRNA) Expression Levels in Pancreatic Cancer Tissue Comparing with Immortalized Pancreatic Duct Epithelial Cells
miRNA HPDE cells Mean±SEM
miRNA-200a 1 266.9±57.3
miRNA-200b 1 18.5±2.2
miRNA-200c 1 0.7±0.1
miRNA-141 1 27.2±6.6
miRNA-205 1 0.1±0.1

HPDE, human pancreatic ductal epithelial; SEM, standard error of the mean.

Table 4.
Prognostic Factors of Pancreatic Cancer
  HR 95% CI p-value
Univariate analysis      
 Age (>60 yr) 1.081 0.652–1.793 0.763
 Sex (male) 1.286 0.794–2.085 0.307
 Margin invasion (positive) 1.249 0.615–2.536 0.539
 pN (positive) 0.955 0.593–1.539 0.850
 Angiolymphatic invasion (positive) 1.314 0.819–2.108 0.258
 Venous invasion (positive) 0.992 0.551–1.788 0.979
 Perineural invasion (positive) 0.953 0.571–1.591 0.854
 Post operative chemotherapy 0.866 0.540–1.390 0.552
 Post operative gemcitabine 0.524 0.279–0.982 0.044
 Post operative radiation therapy 1.036 0.645–1.664 0.883
 High miRNA-200c (>0.65) 1.849 1.131–3.025 0.014
Multivariate analysis      
 Post operative gemcitabine 0.551 0.293–1.036 0.064
 High miRNA-200c (>0.65) 1.771 1.081–2.900 0.023

HR, hazard ratio.

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