The manuscript shall undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form

The manuscript shall undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. the discovery cohort, patients with any C allele in had significantly shorter median progression-free survival (11.3 vs 13.1 months, HR: 1.70, 95% CI: 1.04C2.77, = 0.022) in univariate analysis and overall survival (OS) (27.4 vs 49.9 months, HR: 2.10, 95% CI: 1.07C4.10, = 0.031) in uni- and multivariable analyses than those with the T/T variant. The significant association between and OS was confirmed in the validation cohort (25.8 vs Ophiopogonin D’ 31.6 months, HR: 1.53, 95% CI: Rabbit polyclonal to AKR1D1 1.09C2.15, = 0.013). and in the validation cohort had significant correlations with OS in uni- and multivariable analyses. None of SNPs were significant in the cetuximab control cohort. Conclusion: Selected SNPs in the adenosine pathway may impact clinical outcome of mCRC patients treated with FOLFIRI plus bevacizumab. = 107), the patients treated with FOLFIRI plus bevacizumab in TRIBE as the validation cohort (= 215), and the patients treated with FOLFIRI plus cetuximab in FIRE-3 as unfavorable control cohort (= 129), respectively. Patients without sufficient samples for analysis were excluded. Selection of single nucleotide polymorphisms (SNPs) and genotyping Polymorphisms underlying adenosine-related molecules; CD39 (= 0.006), higher ECOG performance status ( 0.001), higher rates of primary tumor resection ( 0.001), and much lower KRAS ( 0.001) and RAS mutation Ophiopogonin D’ rates ( 0.001). The control cohort had more males than the other two cohorts (= 0.013). Predictive and prognostic values of the adenosine-related SNPs in the discovery cohort Table 1 summarizes associations between the selected adenosine-related SNPs and clinical outcomes. Among the seven candidate SNPs, were significantly associated with clinical outcome in the discovery cohort. Table 1. Ophiopogonin D’ Associations between adenosine-related SNPs and clinical outcomes value was based on the Chi-square test for tumor response, log-rank test for progression-free survival and overall survival in the univariate analysis, and Wald test in the multivariable Cox proportional hazards regression model adjusting for sex, ECOG performance status, liver limited disease, and BRAF status in the discovery and control cohorts; adjusting for sex, age, ECOG performance status, primary tumor site, primary tumor resected, liver limited disease, adjuvant chemotherapy, BRAF status, and RAS status in the validation cohort. Abbreviations: Bev, Bevacizumab; Cet, Cetuximab; SNP, single nucleotide polymorphism. In univariate analysis, mCRC patients with any C allele in had significantly shorter Ophiopogonin D’ median PFS [11.3 vs 13.1 months, hazard ratio (HR): 1.70, 95% confidence intervals (CI): 1.04C2.77, = 0.022] and OS (27.4 vs 49.9 months, HR: 2.19, 95% CI: 1.15C4.14, = 0.012) than those with the T/T variant. (Physique 2A) Other SNPs also had significant differences in OS: patients carrying any A allele in had significantly longer median OS (41.9 vs 23.7 months, HR: 0.50, 95% CI: 0.28C0.91, = 0.017) than those with the G/G variant; patients carrying T/T variant in had significantly longer median OS (49.9 vs 28.1 months, HR: 0.34, 95% CI: 0.14C0.84, = 0.008) than those with any C allele. (Supplementary Physique 1) In multivariable analysis, = 0.080). Besides, all three SNPs remained significant for OS: (HR: 2.10, 95% CI: 1.07C4.10, = Ophiopogonin D’ 0.031), = 0.026), (HR: 0.24, 95% CI: 0.09C0.64, = 0.004). Open in a separate window Physique 2. Overall survivals of patients with was also significantly associated with survival in the validation cohort. In addition, was significantly associated with survivals. (Table 1) Patients with any C allele in had significantly shorter median OS (25.8 vs 31.6 months, HR: 1.50, 95% CI: 1.08C2.09, = 0.014) in univariate analysis, (Figure 2B) and with consistent results in multivariable analysis (HR: 1.53, 95% CI: 1.09C2.15, = 0.013). did not show a significant difference but a trend with PFS in univariate (9.9 vs 9.6 months, HR: 1.30, 95% CI: 0.94C1.80, = 0.100) and multivariable analysis (HR: 1.41, 95% CI:.