Prognostic microRNAs in patients operated for pancreatic cancer.

Abstract

4061 Background: The aim was to identify a panel of microRNAs (miRs) that can predict overall survival (OS) in non-microdissected tissues from patients operated for pancreatic cancer (PC). Methods: MiRs were purified from FFPE cancer tissue without microdissection from 225 patients operated for PC. Expression of miRs was determined using TaqMan Human MicroRNA Array. Univariate selection method and Lasso method were applied before the Cox proportional hazard model to relate miRs to OS. Results: At time of folow-up 196 (87%) of patients were dead. High expression of miR212 and miR675 and low expression of miR148*, miR187 and let7g* could predict OS independent of age, gender, KRASmutation, tumor stage, ASA-score, localization and differentiation of tumor (Table). A nomogram based on the adjusted Cox proportional hazard model was determined for these miRs and a prognostic index (PI) for each patient was calculated. The median survival was 1.09 years (CI 0.98-1.43) when PI was higher than median, compared to 2.23 years (CI 1.84-4.36) when PI was below median. The nine miRs that showed the strongest prediction ability by the Lasso method were miR212, miR675, miR187, miR205, miR944, miR431, miR194*, miR148a*, miR769-5p. Thus four miRs, miR212, 675, 187 and 148a*, were identified as predictors for OS in both statistical methods. High expression of miR675, 450b-5p and 222 and low expression of miR148a* and 146a could also predict 2 years OS independent of clinical characteristics. Conclusions: Several miRs in PC tissue have the potential as new prognostic biomarkers in patients operated for PC. A prognostic index including 5 miRs can separate long term survivors after radical operation from patients with poor survival. Hazard ratios for miRs associated with OS. Unadjusted estimates Adjusted estimates* Overall survival Overall survival miR HR 95% CI P miR HR 95% CI P miR-212 1.54 1.21 1.96 <0.001 miR-212 1.32 1.02 1.72 0.033 miR-675 1.08 1.02 1.14 0.009 miR-675 1.06 1.00 1.14 0.051 miR-148a* 0.92 0.88 0.98 0.006 miR-148a* 0.94 0.88 1.00 0.039 miR-187 0.97 0.94 1.00 0.061 miR-187 0.96 0.93 0.99 0.010 let-7g* 0.83 0.73 0.95 0.006 let-7g* 0.78 0.68 0.90 <0.001 *Adjusted for age, gender, calendar year of operation, KRAS, stage, ASA, localization and diff. of tumor.