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
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
Externí odkaz: