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Updated: Jan 8, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Unlocking Spondin-1 and Spondin-2 as Ultrasound-Responsive Biomarkers in Epidermal Growth Factor Receptor-Mutant
Hai Ou1, Feng Jin2, Chenyang Wang2
1Department of Oncology, Zigong First People's Hospital, Zigong, China.
Abstract:
The development of resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) remains a huge challenge in treating EGFR-mutant non-small-cell lung cancer (NSCLC). Recent improvements in ultrasound-based cancer biotherapies have necessitated the discovery of responsive molecular targets that can improve therapeutic accuracy. This study looks at the diagnostic usefulness and functional importance of spondin-1 (SPON1) and spondin-2 (SPON2) in EGFR-mutated NSCLC, with a focus on their possible response to ultrasound-enhanced therapies. Plasma levels of SPON1 and SPON2 were considerably higher in EGFR-mutant NSCLC patients than in healthy controls. Receiver operating characteristic curve analysis demonstrated that both proteins had good sensitivity and specificity. SPON1 and SPON2 expression were linked with aggressive clinical characteristics such as tumor size (≥5 cm), advanced TNM stage (III-IV), and lymph node involvement. Importantly, both markers were significantly elevated in gefitinib-resistant, EGFR-mutant NSCLC cells. Functional investigations revealed that suppressing SPON1 and SPON2 reversed resistance by inhibiting proliferation and invasion while increasing apoptosis. In contrast, overexpression conferred resistance to gefitinib in parental cells. Given their dual roles in diagnosis and resistance, SPON1 and SPON2 are intriguing ultrasound-responsive biomarkers in EGFR-mutant NSCLC. These findings provide the groundwork for future incorporation of ultrasound-mediated delivery methods or sonodynamic treatments targeting SPON1/SPON2, opening up new possibilities for overcoming EGFR-TKI resistance and improving therapeutic effectiveness in resistant NSCLC.
Insights
Spondin-1 and Spondin-2 are elevated in EGFR-mutant non-small-cell lung cancer (NSCLC) and linked to resistance against EGFR-TKIs. Targeting these proteins may overcome treatment resistance.
Area of Science:
- Oncology
- Biomarker Discovery
- Molecular Biology
Background:
- Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance is a major obstacle in treating EGFR-mutant non-small-cell lung cancer (NSCLC).
- Ultrasound-based therapies require novel molecular targets for enhanced treatment precision.
Purpose of the Study:
- To investigate the diagnostic utility and functional role of spondin-1 (SPON1) and spondin-2 (SPON2) in EGFR-mutant NSCLC.
- To explore the potential of SPON1 and SPON2 as targets for ultrasound-enhanced therapies.
Main Methods:
- Measured plasma levels of SPON1 and SPON2 in EGFR-mutant NSCLC patients and healthy controls.
- Utilized receiver operating characteristic (ROC) curve analysis for diagnostic assessment.
- Correlated protein expression with clinical characteristics and gefitinib resistance.
- Performed functional studies involving suppression and overexpression of SPON1 and SPON2.
Main Results:
- Plasma SPON1 and SPON2 levels were significantly higher in EGFR-mutant NSCLC patients.
- Both proteins demonstrated good diagnostic sensitivity and specificity.
- Elevated SPON1 and SPON2 expression correlated with advanced tumor stage, lymph node involvement, and gefitinib resistance.
- Suppression of SPON1/SPON2 reversed gefitinib resistance, while overexpression induced it.
Conclusions:
- SPON1 and SPON2 serve as promising diagnostic biomarkers for EGFR-mutant NSCLC.
- These proteins are implicated in EGFR-TKI resistance, suggesting them as potential therapeutic targets.
- SPON1 and SPON2 are ultrasound-responsive, paving the way for novel ultrasound-mediated treatment strategies against resistant NSCLC.
