Abstract
BackgroundAngiogenesis plays a pivotal role in malignant tumour growth and the metastatic process. We analysed the prognostic value of two angiogenesis parameters, microRNA-126 (miRNA-126) and microvessel density (MVD), in a population based cohort of patients operated for stage II colon cancer.MethodsA total of 560 patients were included. Analyses were performed on formalin fixed paraffin embedded tissue from the primary tumours. The analysis of miRNA-126 expression was performed by qPCR. Microvessels were visualised by CD105 and quantified in hot spots using a light microscope. The analyses were correlated with recurrence-free cancer specific survival (RF-CSS) and overall survival (OS).ResultsLow miRNA-126 expression was significantly correlated to T4, high malignancy grade, tumour perforation, fixation, and the presence of microsatellite instability. A prognostic impact on OS was detected in the simple analysis favouring patients with high miRNA-126 expression p = 0.03, and borderline significance as to RF-CSS, p = 0.08. The impact on OS demonstrated borderline significance in a following multiple Cox regression analysis, hazard ratio 0.76 (95% confidence interval, 0.58-1.00), p = 0.051. The MVD estimate was not associated with either RF-CSS, p = 0.49, or OS, p = 0.94.ConclusionThe current population based study of patients operated for stage II colon cancer demonstrated correlations between several prognostic unfavourable characteristics and miRNA-126 and argues for a possible prognostic impact on overall survival. An influence on survival by the MVD estimate was not detected.
Highlights
Angiogenesis plays a pivotal role in malignant tumour growth and the metastatic process
The importance of microvessel density (MVD) has been known for two decades [9] and while the majority of the literature seems to support MVD as having prognostic value in various types of cancer, counting of microvessels has never been integrated in the clinic
The median miRNA126 expression was significantly lower in T4 tumours, and in tumours with high malignancy grade, perforation and fixation, or microsatellite instability (MSI)
Summary
Angiogenesis plays a pivotal role in malignant tumour growth and the metastatic process. We analysed the prognostic value of two angiogenesis parameters, microRNA-126 (miRNA-126) and microvessel density (MVD), in a population based cohort of patients operated for stage II colon cancer. Angiogenesis is a classical hallmark of cancer [6] and a prerequisite for the continuous growth of the malignant tumour, and simultaneously it provides an escape route for invasive tumour cells to metastasize [7]. This is reflected in studies demonstrating a relationship between aspects of angiogenesis and the prognosis of patients with cancer. A prospectively planned study of a large population based cohort of patients with stage II colon cancer may provide a definitive and valid evaluation of the clinical potential of this biomarker
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