Germ line polymorphisms of genes involved in pluripotency transcription factors predict efficacy of cetuximab in metastatic colorectal cancer
Autor: | Chiara Cremolini, Volker Heinemann, Joshua Millstein, Wu Zhang, Heinz-Josef Lenz, Natsuko Kawanishi, Hiroyuki Arai, Alfredo Falcone, Shivani Soni, Sebastian Stintzing, Francesca Battaglin, Jingyuan Wang, Fotios Loupakis, Shannon M. Mumenthaler, Priya Jayachandran |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Oncology Cancer Research Time Factors Colorectal cancer Cetuximab Antineoplastic Agents Immunological 0302 clinical medicine Antineoplastic Combined Chemotherapy Protocols Epidermal growth factor receptor Neoplasm Metastasis Randomized Controlled Trials as Topic Tumor biology Nanog Homeobox Protein Single Nucleotide Progression-Free Survival Bevacizumab Phase III as Topic Immunological Phenotype 030220 oncology & carcinogenesis Cohort Neoplastic Stem Cells FOLFIRI Biomarker (medicine) Colorectal Neoplasms medicine.drug medicine.medical_specialty Antineoplastic Agents Single-nucleotide polymorphism Polymorphism Single Nucleotide 03 medical and health sciences Internal medicine Biomarkers Tumor medicine Humans Clinical Trials Genetic Predisposition to Disease Polymorphism Retrospective Studies Biomarker Cancer stem cell NANOG Clinical Trials Phase III as Topic business.industry medicine.disease 030104 developmental biology biology.protein business Biomarkers |
Zdroj: | European Journal of Cancer. 150:133-142 |
ISSN: | 0959-8049 |
Popis: | Cancer stem cells (CSCs) are primarily maintained by a network of pluripotency transcription factors (PTFs). Given a close relationship of CSC regulation with epidermal growth factor receptor and vascular endothelial growth factor signalling, we investigated whether single-nucleotide polymorphisms (SNPs) in PTF genes are related to the efficacy of cetuximab and/or bevacizumab in patients with metastatic colorectal cancer (mCRC).Genomic and clinical data from three independent clinical trial cohorts were tested: cetuximab cohort (FOLFIRI/cetuximab arm in FIRE-3, n = 129), bevacizumab cohort 1 (FOLFIRI/bevacizumab arm in FIRE-3, n = 107) and bevacizumab cohort 2 (FOLFIRI/bevacizumab arm in TRIBE, n = 215). Genomic DNA extracted from blood samples was genotyped, and ten SNPs were tested for association with clinical outcomes.In the cetuximab cohort, four SNPs were significantly associated with progression-free survival in univariate analysis: NANOG rs11055767 (any A allele vs C/C, hazard ratio [HR] = 0.62, 95% confidence interval [CI] = 0.42-0.94, p = 0.02), NANOG rs10744044 (any A allele vs G/G, HR = 0.59, 95% CI = 0.39-0.90, p = 0.01), NANOGP8 rs2168958 (any C allele vs A/A, HR = 2.12, 95% CI = 1.36-3.29, p 0.001) and NANOGP8 rs2279066 (any C allele vs T/T, HR = 1.80, 95% CI = 1.06-1.68, p = 0.03). Multivariate analysis confirmed the significant associations for NANOGP8 rs2168958 and NANOGP8 rs2279066. In either bevacizumab cohort, no significant associations were observed in univariate analysis.Germ line polymorphisms in the PTF genes could be predictive markers for cetuximab in mCRC. |
Databáze: | OpenAIRE |
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