SMAD4 and KCNQ3 alterations are associated with lymph node metastases in oesophageal adenocarcinoma.
Biochim Biophys Acta Mol Basis Dis
; 1870(1): 166867, 2024 01.
Article
em En
| MEDLINE
| ID: mdl-37648039
ABSTRACT
Metastasis in oesophageal adenocarcinoma (OAC) is an important predictor of survival. Radiological staging is used to stage metastases in patients, and guide treatment selection, but is limited by the accuracy of the approach. Improvements in staging will lead to improved clinical decision making and patient outcomes. Sequencing studies on primary tumours and pre-cancerous tissue have revealed the mutational landscape of OAC, and increasingly cheap and widespread sequencing approaches offer the potential to improve staging assessment. In this work we present an analysis of lymph node metastases found by radiological and pathological sampling, identifying new roles of the genes SMAD4 and KCNQ3 in metastasis. Through transcriptomic analysis we find that both genes are associated with canonical Wnt pathway activity, but KCNQ3 is uniquely associated with changes in planar cell polaritiy associated with non-canonical Wnt signalling. We go on to validate our observations in KCNQ3 in cell line and xenograph systems, showing that overexpression of KCNQ3 reduces wound closure and the number of metastases observed. Our results suggest both genes as novel biomarkers of metastatic risk and offer new potential routes to drug targeting.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Esofágicas
/
Adenocarcinoma
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Reino Unido