TWIST1 polymorphisms predict survival in patients with metastatic colorectal cancer receiving first-line bevacizumab plus oxaliplatin-based chemotherapy
Menée sur 220 patients atteints d'un cancer colorectal métastatique traité à l'aide d'une chimiothérapie à base d'oxaliplatine en combinaison avec du bévacizumab ou du cétuximab, cette étude met en évidence une association entre des polymorphismes à simple nucléotide du gène TWIST1 et la survie des patients dont le traitement comporte du bévacizumab
The epithelial-mesenchymal transition (EMT) is an important mechanism of resistance to angiogenesis inhibition. The ability of EMT pathway genetic variants to predict the efficacy of anti-angiogenic therapy is unknown. We analyzed associations between functional single nucleotide polymorphisms (SNPs) in EMT-related genes and outcomes in metastatic colorectal cancer (mCRC) patients undergoing first-line bevacizumab-based chemotherapy. A total of 220 mCRC patients were included in this study: 143 patients treated with first-line bevacizumab-based chemotherapy (bevacizumab cohort) and 77 patients treated with cetuximab-based chemotherapy (cetuximab cohort). SNPs in TWIST1 (rs2285682, rs2285681), ZEB1 (rs10826943, rs2839658), SNAIL (rs1543442, rs4647958), and E-cadherin (rs16260) genes were analyzed by PCR-based direct sequencing. Patients carrying a TWIST1 rs2285682 G allele had a significantly longer median PFS of 18.1 months and OS of 44.1 months compared to those with the T/T genotype, who had a median PFS of 13.3 months (HR, 0.57; P=0.003) and OS of 29.2 months (HR, 0.53; P=0.001) in the bevacizumab cohort. In multivariate analysis, associations between TWIST1 rs2285682 and PFS and OS remained significant. Among women, the G allele of TWIST1 rs2285682 (PFS HR, 0.39, P=0.007; OS HR, 0.30 P=0.001) and TWIST1 rs2285681 (PFS HR, 0.27, P<0.001; OS HR, 0.25 P<0.001) was associated with improved survival. No significant associations were found in the cetuximab cohort. Our findings suggest that TWIST1 polymorphisms are associated with survival in mCRC patients treated with first-line bevacizumab-based chemotherapy and may serve as clinically useful biomarkers for anti-angiogenic therapy.
Molecular Cancer Therapeutics , résumé, 2016