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Clinical Impact of a Novel MicroRNA Chemo-Sensitivity Predictor in Gastrooesophageal Cancer

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Listed:
  • Mette Winther
  • Steen Knudsen
  • Jesper Dahlgaard
  • Thomas Jensen
  • Anker Hansen
  • Peter Buhl Jensen
  • Trine Tramm
  • Jan Alsner
  • Marianne Nordsmark

Abstract

Background: miRNAs might be potentially useful biomarkers for prediction of response to chemotherapeutic agents, radiotherapy and survival. The aim of this retrospective study was to validate miRNA response predictors in a cohort of patients with gastrooesophageal cancer in order to predict overall survival (OS) and disease-specific survival (DSS). Material and Methods: The study population encompassed 53 patients treated with curative intend for loco-regional gastrooesophageal cancer. miRNA expression was quantified from pre-therapeutic and diagnostic, formalin-fixed, paraffin embedded tumour specimens using Affymetrix GeneChip miRNA 1.0 Array. Based on growth inhibition of the NCI60 panel in the presence of cisplatin, epirubicine and capecitabine, a miRNA based response predictor was developed. The Cox proportional hazards model was applied to assess the correlations of the response predictor with OS and DSS. Results: A univariate analysis demonstrated a statistical significant improvement of OS for patients who had undergone surgical resection with prediction scores above the median prediction score (HR: 0.41 (95% CI: 0.17–0.96). Adjusting for surgery and stage, this predictor was identified to be independently associated with both OS (HR: 0.37 (95% CI: 0.16–0.87)) and DSS (HR: 0.32 (0.12–0.87)). Conclusion: The miRNA profile predictive for sensitivity to cisplatin, epirubicine and capecitabine was shown to be independently associated with OS and DSS in patients with gastrooesophageal cancer.

Suggested Citation

  • Mette Winther & Steen Knudsen & Jesper Dahlgaard & Thomas Jensen & Anker Hansen & Peter Buhl Jensen & Trine Tramm & Jan Alsner & Marianne Nordsmark, 2016. "Clinical Impact of a Novel MicroRNA Chemo-Sensitivity Predictor in Gastrooesophageal Cancer," PLOS ONE, Public Library of Science, vol. 11(2), pages 1-8, February.
    • Handle: RePEc:plo:pone00:0148070
    DOI: 10.1371/journal.pone.0148070
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    References listed on IDEAS

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    1. Steen Knudsen & Christoffer Hother & Kirsten Grønbæk & Thomas Jensen & Anker Hansen & Wiktor Mazin & Jesper Dahlgaard & Michael Boe Møller & Elizabeth Ralfkiær & Peter de Nully Brown, 2015. "Development and Blind Clinical Validation of a MicroRNA Based Predictor of Response to Treatment with R-CHO(E)P in DLBCL," PLOS ONE, Public Library of Science, vol. 10(2), pages 1-15, February.
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