Clinical impact of a novel microRNA chemo-sensitivity predictor in gastrooesophageal cancer

Mette Winther; Steen Knudsen; Jesper Ovesen Dahlgaard; Thomas Jensen; Anker Hansen; Peter Buhl Jensen; Trine Tramm; Jan Alsner; Marianne Nordsmark

doi:10.1371/journal.pone.0148070

Clinical impact of a novel microRNA chemo-sensitivity predictor in gastrooesophageal cancer

Mette Winther
, Steen Knudsen
, Jesper Ovesen Dahlgaard
, Thomas Jensen
, Anker Hansen
, Peter Buhl Jensen
, Trine Tramm
, Jan Alsner
, Marianne Nordsmark

Uddannelsesudvikling

Aarhus Univeristy Hospital
Medical Prognosis Institute

Research output: Contribution to journal › Journal article › Research › peer-review

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 locoregional
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.

Original language	English
Article number	2
Journal	P L o S One
Volume	11
Issue number	2
Number of pages	8
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0148070
Publication status	Published - 17 Feb 2016

Keywords

cancer

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10.1371/journal.pone.0148070Licence: CC BY

Cite this

@article{7df24f8f91364956a62c479c8cf2fc58,

title = "Clinical impact of a novel microRNA chemo-sensitivity predictor in gastrooesophageal cancer",

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 locoregional 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. ",

keywords = "cancer",

author = "Mette Winther and Steen Knudsen and Dahlgaard, \{Jesper Ovesen\} and Thomas Jensen and Anker Hansen and \{Buhl Jensen\}, Peter and Trine Tramm and Jan Alsner and Marianne Nordsmark",

year = "2016",

month = feb,

day = "17",

doi = "10.1371/journal.pone.0148070",

language = "English",

volume = "11",

journal = "P L o S One",

issn = "1932-6203",

publisher = "Public Library of Science",

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TY - JOUR

T1 - Clinical impact of a novel microRNA chemo-sensitivity predictor in gastrooesophageal cancer

AU - Winther, Mette

AU - Knudsen, Steen

AU - Dahlgaard, Jesper Ovesen

AU - Jensen, Thomas

AU - Hansen, Anker

AU - Buhl Jensen, Peter

AU - Tramm, Trine

AU - Alsner, Jan

AU - Nordsmark, Marianne

PY - 2016/2/17

Y1 - 2016/2/17

N2 - 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 locoregional 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.

AB - 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 locoregional 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.

KW - cancer

U2 - 10.1371/journal.pone.0148070

DO - 10.1371/journal.pone.0148070

M3 - Journal article

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