Open AccessCytochrome P450 1B1 polymorphism drives cancer cell stemness and patient outcome in head-and-neck carcinoma
Author(s) -
Valérie Le Morvan,
Élodie Richard,
Maud Cadars,
Delphine Fessart,
Léa Broca-Brisson,
Céline Auzanneau,
Alban Pasquies,
A. Modesto,
Amélie Lusque,
Simone MathoulinPélissier,
Amélie Lansiaux,
Jacques Robert
Publication year - 2020
Publication title -
british journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.833
H-Index - 236
eISSN - 1532-1827
pISSN - 0007-0920
DOI - 10.1038/s41416-020-0932-5
Subject(s) - biology , head and neck squamous cell carcinoma , head and neck cancer , cancer research , in vivo , cell growth , cancer , cyp1b1 , medicine , chemotherapy , stem cell , oncology , cytochrome p450 , endocrinology , genetics , metabolism
Background Cytochrome P450 1B1 (CYP1B1) is mostly expressed in tumours and displays unusual properties. Its two polymorphic forms were differently associated with anticancer drug sensitivity. We decipher here the role of this polymorphism in anticancer drug efficacy in vitro, in vivo and in the clinical setting. Methods From head-and-neck squamous cell carcinoma cell lines not expressing CYP1B1, we generated isogenic derivatives expressing the two forms. Proliferation, invasiveness, stem cell characteristics, sensitivity to anticancer agents and transcriptome were analysed. Tumour growth and chemosensitivity were studied in vivo. A prospective clinical trial on 121 patients with advanced head-and-neck cancers was conducted, and a validation-retrospective study was conducted. Results Cell lines expressing the variant form displayed high rates of in vitro proliferation and invasiveness, stemness features and resistance to DNA-damaging agents. In vivo, tumours expressing the variant CYP1B1 had higher growth rates and were markedly drug-resistant. In the clinical study, overall survival was significantly associated with the genotypes, wild-type patients presenting a longer median survival (13.5 months) than the variant patients (6.3 months) ( p = 0.0166). Conclusions This frequent CYP1B1 polymorphism is crucial for cancer cell proliferation, migration, resistance to chemotherapy and stemness properties, and strongly influences head-and-neck cancer patients’ survival.