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Updated: Oct 30, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Sensitivity and optimal clinicopathological features for mutation-targeted liquid biopsy in pN0M0 EGFR-mutant lung
Masaoki Ito1, Yoshihiro Miyata1, Shoko Hirano2
1Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Purpose:
Liquid biopsy for early-stage lung cancer diagnosis is challenging, and optimal candidates' clinicopathological features are unknown. We investigated utility and clinicopathological features of optimal candidates in somatic mutation-targeted liquid biopsy using droplet digital polymerase chain reaction (ddPCR) in pN0M0 EGFR mutation-positive lung adenocarcinoma patients.
Methods:
We performed EGFR mutation-targeted ddPCR liquid biopsy in 100 patients with resected pN0M0 invasive lung adenocarcinoma, whose tumor diameter in high-resolution computed tomography (HRCT) was ≤ 5 cm. Peripheral blood-derived serum was collected preoperatively. Two representative EGFR somatic variants (exon 19 [E746-A750 del (2235_2249 del)]; exon 21 (L858R)) were utilized as liquid biopsy targets. Clinicopathological features including radiological appearance, subhistology, and invasive status were compared between ddPCR-positive and ddPCR-negative patients.
Results:
Among the 100 patients, 98 showed part-solid or pure-solid appearance in HRCT and 2 showed non-solid appearance; 98 were pathological stage IA1-IB. Of the 66 patients with EGFR mutation detection in ddPCR, 12 were significantly positive and 10 (83.3%, 10/12) exhibited pure-solid appearance in HRCT. Clinical invasive tumor ratio was significantly higher in ddPCR-positive than in ddPCR-negative patients (median: 100% vs. 85.4%, P = 0.0212), whereas other clinicopathological features were not significantly different.
Conclusion:
Mutation-targeted liquid biopsy using ddPCR detected lung cancer in 12.0% (12/100) of pN0M0 EGFR-mutant lung adenocarcinoma patients. In 83.3% of the ddPCR-positive patients, tumors showed pure-solid appearance in HRCT. The detection ratio increased to 21.3% (10/47) among patients with pure-solid appearance tumors. Tumor appearance might be useful for better selection of liquid biopsy candidates.
