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. 2017 Dec;17(6):543-550.
doi: 10.1038/tpj.2016.59. Epub 2016 Aug 9.

CXCR4 polymorphism predicts progression-free survival in metastatic colorectal cancer patients treated with first-line bevacizumab-based chemotherapy

S Matsusaka  1 , S Cao  1 , D L Hanna  1 , Y Sunakawa  1 , M Ueno  2 , N Mizunuma  3 , W Zhang  1 , D Yang  1 , Y Ning  1 , S Stintzing  1 , A Sebio  1 , S Stremitzer  1 , S Yamauchi  1 , A Parekh  1 , S Okazaki  1 , M D Berger  1 , R El-Khoueiry  1 , A Mendez  1 , W Ichikawa  4 , F Loupakis  5 , H-J Lenz  1
Affiliations

CXCR4 polymorphism predicts progression-free survival in metastatic colorectal cancer patients treated with first-line bevacizumab-based chemotherapy

S Matsusaka et al. Pharmacogenomics J. 2017 Dec.

Abstract

We analyzed associations between CXCR4/CXCL12 single-nucleotide polymorphisms and outcomes in metastatic colorectal cancer (mCRC) patients who underwent first-line bevacizumab-based chemotherapy. A total of 874 patients were included in this study: 144 treated with bevacizumab and FOLFOX or XELOX (training cohort), 653 treated with bevacizumab and FOLFIRI or FOLFOXIRI (validation cohort A or B) and 77 treated with cetuximab- and oxaliplatin-based regimens (control cohort). One CXCR4 polymorphism (rs2228014) and two CXCL12 polymorphisms (rs1801157 and rs3740085) were analyzed by PCR-based direct sequencing. Patients with a C/C genotype had a prolonged progression-free survival (PFS) compared with those with any T allele (P=0.030) in the training cohort. Similarly, patients with the C/C genotype had a superior PFS in the validation cohorts, but not in the control cohort. Our findings suggest that a common genetic variant, CXCR4 rs2228014, could predict PFS and may guide therapeutic decisions in mCRC patients receiving first-line bevacizumab-based chemotherapy.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Comparison of clinical outcomes by CXCR4 rs2228014 genotype in the training and validation cohorts. Progression-free survival probability in (a) training cohort, (b) validation cohort A and (c) validation cohort B.
Figure 2.
Figure 2.
Hypoxia-inducible factor-1α (HIF-1α) is activated as a result of hypoxia induced by bevacizumab therapy. HIF-1α then upregulates CXCR4 expression that, along with interactions between CXCR4 and its ligand CXCL12, plays an important role in angiogenesis and cancer cell migration.
See this image and copyright information in PMC

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