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Expression Level of Wnt5a Was Related to the Therapeutic Effects of First-Generation EGFR-TKIs

Hai Zhang1, Xiaohua Yang2, Fang Hu1

  • 1Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China.

Oncotargets and Therapy
|July 2, 2020
PubMed
Abstract

Insights

High Wnt5a expression correlates with resistance to first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma patients with EGFR mutations. This finding may help predict treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • First-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective for lung adenocarcinoma with EGFR mutations.
  • Mechanisms of resistance to EGFR-TKIs remain incompletely understood.
  • Wnt5a's role in EGFR-TKI resistance requires further elucidation.

Purpose of the Study:

  • To investigate the association between Wnt5a expression levels and the therapeutic efficacy of first-generation EGFR-TKIs.
  • To explore Wnt5a as a potential biomarker for predicting treatment response in lung adenocarcinoma patients with sensitive EGFR mutations.

Main Methods:

  • Retrospective analysis of 75 lung adenocarcinoma patients treated with first-generation EGFR-TKIs.
  • Classification of patients into effective (progression-free survival > 26 months) and ineffective (progression-free survival < 5 months) groups.
  • Detection of Wnt5a expression using immunofluorescence, immunohistochemistry, and RT-PCR.

Main Results:

  • Wnt5a expression was significantly higher in the ineffective group compared to the effective group (P=0.0216 via immunohistochemistry, P=0.0135 via RT-PCR).
  • Immunofluorescence confirmed Wnt5a localization.
  • A higher Wnt5a level was associated with resistance to first-generation EGFR-TKIs.

Conclusions:

  • Wnt5a expression levels are significantly associated with therapeutic effects of first-generation EGFR-TKIs in lung adenocarcinoma patients with EGFR mutations.
  • Elevated Wnt5a may indicate a poorer response to first-generation EGFR-TKIs, suggesting its potential as a predictive biomarker.
Keywords:
Wnt5aepidermal growth factor receptor mutationtherapeutic effecttyrosine-kinase inhibitors

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