52 Down-regulated         miR-217 2.88±1.15 10.35±3.68 <0.001 3.91±1.36 miR-148a 3.85±1.48 10.39±2.97 <0.001 2.86±0.77 miR-375 4.00±1.55 7.05±1.99 <0.001 1.76±0.36 Data are expressed as the mean ± SD. N: matched normal pancreatic tissue. Determination of prognostic significance of the candidate miRNAs in PDAC The clinicopathological

characteristics of 78 PDAC Torin 1 patients are shown in Table 9. The expression levels of individual miRNAs along with other well-known potential prognostic clinicopathological factors, such as histology, T category, lymph node metastasis, tumour size, perineural MEK162 invasion, venous invasion and margin were included in a univariate analysis. With respect to the miRNA expression levels, for the up-regulated miRNAs, a fold-change of ≥2 was defined as high expression, and a fold-change of <2 was defined as low expression; for the down-regulated miRNAs, a fold-change of ≥2 was defined as low expression, and a fold-change of <2 was defined as high expression. Patients with advanced disease (UICC stage IV and concomitance of distant metastases) were excluded because we assumed that the prognosis of these patients (n=8) is determined by the occurrence of relapse or metastasis rather than other biological

characteristics, such as miRNA expression levels. Table 9 Clinicopathological characteristics of 78 PDAC patients Gender   Male 44 (56%) Female 34 (44%) T category   T1 14 (18%) T2 26 (33%) T3 28 (36%) T4 10 (13%) N category   NO 34 (44%) N1 44 (56%) M category   M0 70 (90%) M1 8 (10%) Tumour size   ≥2 cm 42 (54%) VS-4718 solubility dmso <2 cm 36 (46%) Histology   Well or moderately differentiated 38 (49%) Poorly differentiated 40 (51%) Perineural invasion   None or slight 46 (59%) Prominent 32 (41%) Venous invasion   None or slight 40 (51%) Prominent 38 (49%) Tumour grade (UICC)   Stage I-IIA 32 (41%) Stage IIB-IV 46 (59%) Resection margin status   R0 32 (41%) R1 46 (59%) Kaplan-Meier survival analysis was used to analyse the association between postoperative survival and the miRNA expression

level, and the resulting curves were divided into two classes (high and low expression in comparison with the mean level of miRNA expression as the threshold), as shown in Figure 2. Figure 2 Kaplan-Meier analysis of overall survival in patients with PDAC based on their ID-8 expression of miR-155 (A), miR-100 (B), miR-21 (C), miR-221 (D), miR-31 (E), miR-143 (F), miR-23a (G), miR-217 (H), miR-148a (I) and miR-375 (J). p-values are based on the log-rank test. A univariate analysis using the Cox hazard regression model demonstrated that a high expression level of miR-21 (p=0.018, HR=2.610; 95% CI=1.179-5.777) and miR-155 (p=0.035, HR=2.414; 95% CI=1.064-5.478), a low expression level of miR-375 (p=0.022, HR=2.337; 95% CI=1.431-5.066), T category (p=0.039, HR=2.282; 95% CI=1.043-4.994) and margin involvement (p=0.026, HR=2.550; 95% CI=1.120-5.805) are associated with poor patient survival.