Type

Journal Article

Authors

Ruben Postel
William M Gallagher
Laurens G van der Flier
Annette T Byrne
Bauke Ylstra
Nicole C T van Grieken
Arjan W Griffioen
Jochen H M Prehn
Timo Gaiser
Matthias P Ebert
and 16 others

Subjects

Biochemistry

Topics
colorectal cancer crc dna microarray transcriptional profiling endothelial cells colorectal cancer dna profiling differentially expressed genes mrna expression

Apelin: A putative novel predictive biomarker for bevacizumab response in colorectal cancer. (2016)

Abstract Bevacizumab (bvz) is currently employed as an anti-angiogenic therapy across several cancer indications. Bvz response heterogeneity has been well documented, with only 10-15% of colorectal cancer (CRC) patients benefitting in general. For other patients, clinical efficacy is limited and side effects are significant. This reinforces the need for a robust predictive biomarker of response. To identify such a biomarker, we performed a DNA microarray-based transcriptional profiling screen with primary endothelial cells (ECs) isolated from normal and tumour colon tissues. Thirteen separate populations of tumour-associated ECs and 10 of normal ECs were isolated using fluorescence-activated cell sorting. We hypothesised that VEGF-induced genes were overexpressed in tumour ECs; these genes could relate to bvz response and serve as potential predictive biomarkers. Transcriptional profiling revealed a total of 2,610 differentially expressed genes when tumour and normal ECs were compared. To explore their relation to bvz response, the mRNA expression levels of top-ranked genes were examined using quantitative PCR in 30 independent tumour tissues from CRC patients that received bvz in the adjuvant setting. These analyses revealed that the expression of MMP12 and APLN mRNA was significantly higher in bvz non-responders compared to responders. At the protein level, high APLN expression was correlated with poor progression-free survival in bvz-treated patients. Thus, high APLN expression may represent a novel predictive biomarker for bvz unresponsiveness.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Ruben Postel, William M Gallagher, Laurens G van der Flier, Annette T Byrne, Bauke Ylstra, Nicole C T van Grieken, Arjan W Griffioen, Jochen H M Prehn, Timo Gaiser, Matthias P Ebert and 16 others

Experts in our system

1
William M Gallagher
University College Dublin
Total Publications: 148
 
2
Annette T Byrne
Royal College of Surgeons in Ireland
Total Publications: 41
 
3
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206