Abstract
BackgroundmiRNAs 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 MethodsThe 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.ResultsA 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)).ConclusionThe 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.
Highlights
Chemo- and radiotherapy are essential therapeutic strategies for cancer treatment
A univariate analysis demonstrated a statistical significant improvement of overall survival (OS) for patients who had undergone surgical resection with prediction scores above the median prediction score
Adjusting for surgery and stage, this predictor was identified to be independently associated with both OS (HR: 0.37) and disease-specific survival (DSS) (HR: 0.32 (0.12–0.87))
Summary
Chemo- and radiotherapy are essential therapeutic strategies for cancer treatment. due to intrinsic or acquired treatment resistance, chemo- and radiotherapy fail to eliminate all tumour cells [1]. MiRNAs are small, endogenous, non-coding RNAs that act as posttranscriptional regulators, targeting mRNA for degradation or translational repression [3]. MicroRNAs (miRNAs) are biomarkers with a significant potential due to both tissue-specificity and aberrant expression in tumour cells [2]. 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)
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