Abstract LB-174: MicroRNA-126 (miR-126) and epidermal growth factor-like domain 7 (EGFL7) in Bevacizumab-treated patients with metastatic colorectal cancer
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E-Article
Title:
Abstract LB-174: MicroRNA-126 (miR-126) and epidermal growth factor-like domain 7 (EGFL7) in Bevacizumab-treated patients with metastatic colorectal cancer
Description:
Abstract The miR-126 gene is located within intron 7 of the EGFL7 encoding gene, and therefore miR-126 expression is dependent on the transcription of the EGFL7 gene. It has been suggested that transcription is regulated by the VEGFR pathway through Ets1 transcription factor, that miR-126 itself negatively regulates the VEGF-R signaling pathway, and that EGFL7 itself regulates Notch signaling. In cancer therapeutic settings, VEGF or VEGF-R directed therapies are thus likely to affect expression of EGFL7 and miR-126. In colorectal cancer (CRC) tissue, miR-126 and EGFL7 are highly expressed in endothelial cells. In studies of XELOX-treated patients, we have previously reported that the miR-126 expression level measured by quantitative in situ hybridization (qISH) is related to poor response (Hansen et al, BMC Cancer 2012, 12:83). Here, we have analyzed miR-126 and EGFL7 expression by qISH and quantitative immunohistochemistry (qIHC), respectively, in 158 patients from two different cohorts with mCRC after treatment with anti-VEGF therapy (Bevacizumab) in combination with chemotherapy. We found that the EGFL7 vessel area (VA) in primary tumors was closely related to treatment response with a median EGFL7 VA in responding patients of 4 (95% CI 4-6) compared to 8.5 (95% CI 7-11) in non-responders, p<0.001. This difference translated into a borderline significant difference in progression-free survival (PFS, p=0.06). Furthermore, a significant relationship between high EGFL7 VA and KRAS mutation was detected (p<0.05). The results showed no significant relationship between the miR-126 VA and the clinical endpoints. Our study suggests a predictive value of EGFL7 in regard to first-line chemotherapy and bevacizumab in patients with mCRC. The strong predictive value of miR-126 found in mCRC patients treated with chemotherapy only was absent, suggesting that the anti-VEGF directed therapy is likely to have affected a key role of miR-126 in regulating the VEGFR pathway. Citation Format: Boye S. Nielsen, Flemming B. Sorensen, Anders Johnsson, Anders Jakobsen, Torben F. Hansen. MicroRNA-126 (miR-126) and epidermal growth factor-like domain 7 (EGFL7) in Bevacizumab-treated patients with metastatic colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-174. doi:10.1158/1538-7445.AM2014-LB-174