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Prognostic MicroRNAs in Cancer Tissue from Patients Operated for Pancreatic Cancer—Five MicroRNAs in a Prognostic Index

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Abstract

Background

The aim of the present study was to identify a panel of microRNAs (miRNAs) that can predict overall survival (OS) in non micro-dissected cancer tissues from patients operated for pancreatic cancer (PC).

Methods

MiRNAs were purified from formalin-fixed paraffin embedded (FFPE) cancer tissue from 225 patients operated for PC. Only a few of those patients received adjuvant chemotherapy. Expressions of miRNAs were determined with the TaqMan MicroRNA Array v2.0. Two statistical methods, univariate selection and the Lasso (Least Absolute Shrinkage and Selection Operator) method, were applied in conjunction with the Cox proportional hazard model to relate miRNAs to OS.

Results

High expression of miR-212 and miR-675 and low expression of miR-148a*, miR-187, and let-7g* predicted short OS independent of age, gender, calendar year of operation, KRAS mutation status, tumor stage, American Society of Anesthesiologists (ASA) score, localization (not miR-148a*), and differentiation of tumor. A prognostic index (PI) based on these five miRNAs was calculated for each patient. The median survival was 1.09 years (Confidence Interval [CI] 0.98–1.43) for PI > median PI compared to 2.23 years (CI 1.84–4.36) for PI < median. MiR-212, miR-675, miR-187, miR-205, miR-944, miR-431, miR-194*, miR-148a*, and miR-769-5p showed the strongest prediction ability by the Lasso method. Thus miR-212, miR-675, miR-187, and miR-148a* were predictors for OS in both statistical methods.

Conclusions

The combination of five miRNAs expression in non micro-dissected FFPE PC tissue can identify patients with short OS after radical surgery. The results are independent of chemotherapy treatment. Patients with a prognostic index > median had a very short median OS of only 1 year.

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Acknowledgments

This work was supported by Grants from the Research Council at Herlev Hospital and two private funds: the “Augustinus Fonden” and the “Læge Sofus Carl Emil Friis og hustru Olga Doris Friis’ Legat.” The funding organizations had no role in the study design, data collection and analysis, the decision to publish, or the preparation of the manuscript. The authors are grateful to molecular biologist Mel Herein and technicians Krisztina Faludi and Eileen Wong of Herlev Hospital, Copenhagen University Hospital, for help with the sectioning of the samples, and to Mogens Kruhøffer from AROS, Applied Biotechnology A/S, Aarhus, Denmark, who provided excellent technical assistance with the microRNA array analysis.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Surgical Gastroenterology and Transplantation, Copenhagen University Hospital, C 2-12-2, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Nicolai A. Schultz

  2. Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark

    Klaus K. Andersen & Anne Roslind

  3. Division of Surgery, Department of Pathology, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark

    Hanni Willenbrock

  4. Exiqon, Vedbaek, Denmark

    Hanni Willenbrock

  5. Division of Surgery, Department of Gastroenterology, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark

    Morten Wøjdemann

  6. Departments of Oncology and Medicine, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark

    Julia S. Johansen

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  1. Nicolai A. Schultz
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Corresponding author

Correspondence to Nicolai A. Schultz.

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Supplementary Figure 1

CONSORT diagram. (JPG 119kb)

Supplementary Figure 2

Nomogram for the multivariate survival model predicting OS in patients operated for PC. To estimate risk, calculate points for each miRNA expression in PC tissue by drawing a straight line from patients miRNA to the axis labeled “points.” Sum all points and draw a straight line from the total point axis to the 3-month, 1-year, and 10-year survival probability axes. (DOC 26 kb)

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Schultz, N.A., Andersen, K.K., Roslind, A. et al. Prognostic MicroRNAs in Cancer Tissue from Patients Operated for Pancreatic Cancer—Five MicroRNAs in a Prognostic Index. World J Surg 36, 2699–2707 (2012). https://doi.org/10.1007/s00268-012-1705-y

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