A Genetic Variant in CD274 Is Associated With Prognosis in Metastatic Colorectal Cancer Patients Treated With Bevacizumab-Based Chemotherapy

Abstract

Bevacizumab plus chemotherapy is a well-established first-line treatment for metastatic colorectal cancer (mCRC). We investigated whether polymorphisms of genes involved in immune regulation signaling are related to the clinical outcome of mCRC patients treated with bevacizumab-based chemotherapy. In this study, we genotyped 14 single-nucleotide polymorphisms (SNP) in IFN-γ/IFNGRs/JAKs/STATs/PD-L1 pathway by using DNA from blood samples of 141 mCRC patients treated with first-line bevacizumab-based chemotherapy. In the univariate and multivariate analysis, patients with AA genotype of CD274:rs2297136 had a significantly better PFS and OS than patients with AG or GG genotype (10.8 versus 9.8, log-rank P=0.0031; 31.4 versus 20.9, log-rank P=0.0233). Patients with AG/GG genotype of IFNGR1:rs2234711, CT/TT genotype of IFNGR1:rs9376267 also showed longer OS than patients with AA or CC genotype, however, the statistic did not reach significant after adjusted by clinical factors in the multivariate analysis. A nomogram based on the genetic variants and clinic characteristics was developed with a good accuracy to predict patients’ survival. Our result indicates that CD274:rs2297136 is one of the most important predictors for the prognosis of mCRC patients treated with bevacizumab-based chemotherapy, if further validated in larger population.