Dataset Information

Prognostic importance of circulating epidermal growth factor-like domain 7 in patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab.

ABSTRACT: High tumor expression of epidermal growth factor-like domain 7 (EGFL7) has been associated with a poor prognosis in colorectal cancer. The aim of the current study was to investigate the possible prognostic impact of circulating EGFL7 (cir-EGFL7), combined with single nucleotide polymorphism (SNP) analyses, in patients with metastatic colorectal cancer (mCRC) treated with first line chemotherapy and bevacizumab. A total of 88 patients were included. Serum was collected prior to treatment initiation, at first evaluation after 3 weeks, and at progression. Cir-EGFL7 was analysed by the enzyme-linked immunosorbent assay (ELISA) technique. The SNPs were analysed by real-time qPCR based on DNA from whole blood. Endpoints were response rate (RR), progression free survival (PFS), and overall survival (OS). Cir-EGFL7 decreases after administration of chemotherapy plus bevacizumab. Baseline levels of cir-EGFL7 were significantly related to PFS and OS, p?=?0.0431 and p?=?0.0017, respectively, with increasing cir-EGFL7 levels associated with a worse prognosis. Circulating EGFL7 was not associated with RR. The SNP analyses revealed a significant relationship between rs1051851 and OS, p?=?0.030. This study demonstrates that cir-EGFL7 changes during treatment with chemotherapy plus bevacizumab and that baseline levels and genetic variations may influence the overall prognosis of patients with mCRC. The findings call for further validation.

SUBMITTER: Hansen TF

PROVIDER: S-EPMC5443778 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Prognostic importance of circulating epidermal growth factor-like domain 7 in patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab.

Hansen Torben Frøstrup TF Andersen Rikke Fredslund RF Olsen Dorte Aalund DA Sørensen Flemming Brandt FB Jakobsen Anders A

Scientific reports 20170524 1

High tumor expression of epidermal growth factor-like domain 7 (EGFL7) has been associated with a poor prognosis in colorectal cancer. The aim of the current study was to investigate the possible prognostic impact of circulating EGFL7 (cir-EGFL7), combined with single nucleotide polymorphism (SNP) analyses, in patients with metastatic colorectal cancer (mCRC) treated with first line chemotherapy and bevacizumab. A total of 88 patients were included. Serum was collected prior to treatment initiat ...[more]

PMID: 28539619

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Project description:BACKGROUND:No biomarkers exist to predict benefit from antiangiogenic therapy in metastatic colorectal cancer patients. ACVRL1 (activin receptor like-protein 1) encodes for ALK1, a member of the transforming growth factor-? receptor family, which directs pathologic angiogenesis. We examined the intratumoral expression of ACVRL1 and other angiogenesis pathway-related genes to identify molecular markers in the TRIBE study. MATERIALS AND METHODS:Of 503 randomized patients, 228 had sufficient tissue for analysis. Formalin-fixed paraffin-embedded specimens were examined for expression of VEGF-A, VEGF-B, VEGF-C, VEGFR1, VEGFR2, ACVRL1, EphB4, and EGFL7 using reverse transcription polymerase chain reaction. A maximal ?2 approach was used to determine the messenger RNA levels associated with progression-free survival (PFS), overall survival (OS), response rate, early tumor shrinkage, and depth of response. Recursive partitioning trees were constructed to identify composite prognostic biomarker profiles. External validation was conducted in silico using the Oncomine database. RESULTS:High ACVRL1 expression was associated with superior OS in both treatment arms (FOLFOXIRI [5-fluorouracil, leucovorin, oxaliplatin, irinotecan]-bevacizumab, 32.7 vs. 13.5 months, hazard ratio [HR], 0.38, P = .023; FOLFIRI [5-fluorouracil, leucovorin, irinotecan]-bevacizumab, 35.1 vs. 22.0 months, HR, 0.36, P = .006) and prolonged PFS (11.7 vs. 5.9 months, multivariate HR, 0.17; P = .001) for patients receiving FOLFOXIRI-bevacizumab on univariate and multivariate analyses. In recursive partitioning analysis, ACVRL1 was the strongest discriminator of the response rate, PFS, and OS in patients receiving FOLFOXIRI-bevacizumab and of OS in patients receiving FOLFIRI-bevacizumab. In silico validation revealed significant associations between ACVRL1 expression, disease recurrence, and 1-year survival (P < .05) among all colorectal cancer stages. CONCLUSION:ACVRL1 expression could serve as a prognostic biomarker in metastatic colorectal cancer patients receiving chemotherapy and bevacizumab and warrants further evaluation in prospective studies.

Dataset Information

Prognostic importance of circulating epidermal growth factor-like domain 7 in patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab.

Publications

Prognostic importance of circulating epidermal growth factor-like domain 7 in patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab.

Similar Datasets

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