Oncogene HSPH1 modulated by the rs2280059 genetic variant diminishes EGFR-TKIs efficiency in advanced lung adenocarcinoma.
Carcinogenesis
; 41(9): 1195-1202, 2020 09 24.
Article
em En
| MEDLINE
| ID: mdl-32815538
ABSTRACT
Although epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy is effective for most advanced non-small-cell lung cancer (NSCLC) patients with mutant EGFR, some patients show little or no response. Germline variations, such as single-nucleotide polymorphisms (SNPs), have been proved to be involved in disease progression after EGFR-TKI therapy. In this study, we hypothesized that the functional HSPH1 SNP may affect gene expression and, thus, prognosis of NSCLC patients treated with EGFR-TKIs. We systematically examined impacts of HSPH1 SNPs on NSCLC survival in two independent cohorts consisted of 319 EGFR-TKI treated stage IIIB/IV NSCLC patients. The promoter rs2280059 polymorphism was significantly associated with patient survival in both cohorts. In vitro and In vivo assays elucidated that rs2280059 G allele shows higher capability to drive HSPH1 promoter activities. Silencing HSPH1 significantly increases the antineoplastic effects of gefitinib on NSCLC cells. Our findings demonstrated potential implications of HSPH1 in clinic, which may lead to better understanding and outcome assessment of EGFR-TKI treatment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
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Regulação Neoplásica da Expressão Gênica
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Carcinoma Pulmonar de Células não Pequenas
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Proteínas de Choque Térmico HSP110
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Gefitinibe
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Mutação
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Carcinogenesis
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China