Genetic variations in angiopoietin and pericyte pathways and clinical outcome in patients with resected colorectal liver metastases. Issue 11 (17th February 2015)

• Record Type: Journal Article
• Authors: Stremitzer, Stefan; Zhang, Wu; Yang, Dongyun; Ning, Yan; Stintzing, Sebastian; Sebio, Ana; Sunakawa, Yu; Yamauchi, Shinichi; Matsusaka, Satoshi; El‐Khoueiry, Rita; Stift, Judith; Wrba, Friedrich; Gruenberger, Thomas; Lenz, Heinz‐Josef
• Is Part Of: Cancer. Volume 121:Issue 11(2015)
• Page Start: 1898
• Page End: 1905
• Publication Date: 2015-02-17
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.29259
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr29259-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Genes involved in the angiopoietin and pericyte pathways may become escape mechanisms under antivascular endothelial growth factor (anti‐VEGF) therapy. The authors investigated whether variations within genes in these pathways are associated with clinical outcome in patients with colorectal liver metastases who undergo liver resection and receive perioperative, bevacizumab‐based chemotherapy.</p> </sec> <sec id="cncr29259-sec-0002" sec-type="section"> <title>METHODS</title> <p>Single nucleotide polymorphisms (SNPs) in 9 genes (angiopoietin‐1 [<italic>ANGPT1</italic>]; <italic>ANGPT2</italic>; TEK tyrosine kinase, endothelial [<italic>TEK</italic>]; platelet‐derived growth factor β [<italic>PDGFB</italic>]; β‐type platelet‐derived growth factor receptor [<italic>PDGFRB</italic>]; insulin‐like growth factor 1 [<italic>IGF1</italic>]; transforming growth factor β1 [<italic>TGFB1</italic>]; RalA binding protein 1 [<italic>RALBP1</italic>]; and regulator of G‐protein signaling 5 [<italic>RGS5</italic>]) were analyzed in samples of genomic DNA from 149 patients and were evaluated for associations with clinical outcome.</p> </sec> <sec id="cncr29259-sec-0003" sec-type="section"> <title>RESULTS</title> <p> <italic>RALBP1</italic> reference SNP 329007 (rs329007) A>G resulted in a significant difference in recurrence‐free survival (A/A genotype, 14.0 months; A/G or G/G genotype, 9.2 months; hazard ratio [HR], 1.60; <italic>P</italic> = .024). <italic>PDGFB</italic> rs1800818 A>G was associated with 3‐year overall survival rates (A/A genotype, 78%; A/G genotype, 69%; [HR 1.37]; G/G genotype, 53%; [HR 2.12]; <italic>P</italic> = .048). In multivariate analysis, <italic>RALBP1</italic> rs329007 A>G remained significant (HR, 1.99; <italic>P</italic> = .002). <italic>PDGFB</italic> rs1800818 A>G and <italic>RALBP1</italic> rs329007 A>G were correlated with radiologic response (A/A or A/G genotype, 86%; G/G genotype, 71% [<italic>P</italic> = .042]; A/A genotype, 78%; A/G or G/G genotype, 94% [<italic>P</italic> = .018], respectively). <italic>RALBP1</italic> rs329007 A>G demonstrated significantly different rates of histologic response (A/A genotype: major histologic response, 35%; partial histologic response, 34%; no histologic response, 30%; A/G or G/G genotype: 46%, 13%, and 41%, respectively; <italic>P</italic> = .029). Recursive partitioning analysis revealed that <italic>ANGPT2</italic> rs2442599 T>C and <italic>RALBP1</italic> rs329007 A>G were the main SNPs that predicted histologic response and recurrence‐free survival, whereas <italic>PDGFB</italic> rs1800818 A>G was the leading SNP that predicted overall survival. <italic>ANGPT2</italic> rs2916702 C>T and rs2442631 G>A were significantly associated with the probability of achieving a cure.</p> </sec> <sec id="cncr29259-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>The current data suggest that variations in genes involved in the angiopoietin and pericyte pathways may be predictive and/or prognostic biomarkers in patients with resected colorectal liver metastases who receive bevacizumab‐based chemotherapy. <bold><italic>Cancer</italic> 2015;121:1898–1905.</bold> © <italic>2015 American Cancer Society</italic>.</p> </sec> </abstract>