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Supplementary Table 1, Supplementary Table 2A, Supplementary Table 2B, Supplementary Table 3, Supplementary Table 4, or Supplementary Table 5 from TWIST1 Polymorphisms Predict Survival in Patients with Metastatic Colorectal Cancer Receiving First-Line Bevacizumab plus Oxaliplatin-Based Chemotherapy

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posted on 2023-04-03, 14:42 authored by Satoshi Matsusaka, Wu Zhang, Shu Cao, Diana L. Hanna, Yu Sunakawa, Ana Sebio, Masashi Ueno, Dongyun Yang, Yan Ning, Anish Parekh, Satoshi Okazaki, Martin D. Berger, Wataru Ichikawa, Nobuyuki Mizunuma, Heinz-Josef Lenz

Supplementary Table 1. Summary of EMT-related SNPs Supplementary Table 2A. Association between baseline characteristics and clinical outcomes in the bevacizumab cohort Supplementary Table 2B. Association between baseline characteristics and clinical outcomes in the cetuximab cohort Supplementary Table 3. Association between TWIST1 rs2285682 and clinical outcomes in KRAS wild-type and mutant subgroups among the bevacizumab cohort Supplementary Table 4. Association between EMT-related SNPs and clinical outcomes stratified by gender in the bevacizumab cohort Supplementary Table 5. Association between TWIST1 rs2285682 and clinical outcomes in the cetuximab cohort

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NCI

Takashi Tsuruo Memorial

Swiss Cancer League

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ARTICLE ABSTRACT

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 antiangiogenic therapy is unknown. We analyzed associations between functional 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 progression-free survival (PFS) of 18.1 months and overall survival (OS) of 44.1 months compared with 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 antiangiogenic therapy. Mol Cancer Ther; 15(6); 1405–11. ©2016 AACR.

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    Molecular Cancer Therapeutics

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    Gastrointestinal CancersColorectal cancerStem Cell Biology

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