Abstract
BackgroundUnderstanding the biological properties of potential drug targets are important. This is especially true for anti-angiogenic therapies in the search for potential biomarkers. The aim of the present descriptive study was to analyse the intra-tumoural expressions of epidermal growth factor-like domain 7 (EGFL7) and microRNA-126 (miRNA-126) in primary tumours from patients with stage II-IV colorectal cancer (CRC) and in paired samples of primary tumours, regional lymph node metastases and distant metastases.MethodsA total of 126 patients were included. Analyses were performed on resections of primary tumours, regional lymph node metastases, and large needle biopsies from distant metastases. EGFL7 was analysed by immunohistochemistry (IHC) and miRNA-126 by in situ hybridization (ISH). Both biomarkers were quantified by image guided analyses to determine the relative fraction estimates of vessel areas (VA).ResultsThe intra-tumoural EGFL7 VA was significantly higher in primary tumours from patients with recurrent disease than in patients without relapse in both stage II and III, p = 0.019 and p = 0.001, respectively. The EGFL7 VA was significantly higher and the miRNA-126 VA significantly lower in regional lymph node metastases compared to primary tumours, p = 0.01 and p < 10−6, respectively. Furthermore, the miRNA-126 VA in liver metastases was significantly lower than in the primary tumours, p = 0.02.ConclusionThe intra-tumoural expression of EGFL7 in early stages of CRC may influence the risk of post-surgical recurrence. Differential expression of miRNA-126 seems more pronounced in disseminated disease, which supports its role as a regulator in the metastatic process.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0359-y) contains supplementary material, which is available to authorized users.
Highlights
Understanding the biological properties of potential drug targets are important
The intra-tumoural expression of epidermal growth factor-like domain 7 (EGFL7) in early stages of colorectal cancer (CRC) may influence the risk of post-surgical recurrence
We have previously shown that high miRNA-126 expression in primary tumours, determined by in situ hybridization (ISH) analysis, is predictive of response to chemotherapy in metastatic colorectal cancer (mCRC) [25], and that this association is related to miRNA-126 and not the general vascular density in the tumours [27], indicating that the miRNA-126 related vascularisation of primary tumours is an important predictor of response to therapeutic intervention
Summary
Understanding the biological properties of potential drug targets are important. This is especially true for anti-angiogenic therapies in the search for potential biomarkers. The aim of the present descriptive study was to analyse the intra-tumoural expressions of epidermal growth factor-like domain 7 (EGFL7) and microRNA-126. Targeting angiogenesis is a well established strategy in the treatment of patients with metastatic colorectal cancer (mCRC) and the clinical benefit is well documented [1,2]. The clinical benefit, of targeting VEGF-A is rather limited and may be restricted to a subgroup of patients, and new strategies for controlling tumour angiogenesis are constantly being evaluated. Currently under investigation in clinical trials, is the targeting of another important pro-angiogenic protein, the epidermal growth factor-like domain 7 (EGFL7).
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