Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Analysis Center of Life Science, Natural Science Center for Basic Research and Development, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
J Cancer Res Clin Oncol. 2022 Jun;148(6):1419-1428. doi: 10.1007/s00432-021-03721-4. Epub 2021 Jul 3.
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.
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.
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.
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.
液体活检在早期肺癌诊断中具有挑战性，且最佳候选者的临床病理特征尚不清楚。我们使用液滴数字聚合酶链反应（ddPCR）对 EGFR 突变阳性的 pN0M0 肺腺癌患者进行了靶向体细胞突变的液体活检，研究了其在液体活检中的效用和最佳候选者的临床病理特征。
我们对 100 例接受手术切除的 pN0M0 浸润性肺腺癌患者进行了 EGFR 突变靶向 ddPCR 液体活检，这些患者的高分辨率计算机断层扫描（HRCT）肿瘤直径≤5cm。术前采集外周血衍生血清。利用两个代表性的 EGFR 体细胞变异（外显子 19 [E746-A750del（2235_2249del）]；外显子 21 [L858R]）作为液体活检的靶标。比较 ddPCR 阳性和 ddPCR 阴性患者的影像学表现、亚组织学和浸润状态等临床病理特征。
在 100 例患者中，98 例 HRCT 表现为部分实性或纯实性，2 例表现为非实性；98 例为病理分期 IA1-IB。在 ddPCR 检测的 66 例 EGFR 突变患者中，12 例明显阳性，其中 10 例（83.3%，10/12）HRCT 表现为纯实性。ddPCR 阳性患者的临床浸润性肿瘤比例明显高于 ddPCR 阴性患者（中位数：100%比 85.4%，P=0.0212），而其他临床病理特征无显著差异。
ddPCR 检测的靶向液体活检在 12.0%（12/100）的 pN0M0 EGFR 突变肺腺癌患者中发现了肺癌。在 83.3%的 ddPCR 阳性患者中，HRCT 显示肿瘤为纯实性。在纯实性肿瘤患者中，检测率增加到 21.3%（10/47）。肿瘤表现可能有助于更好地选择液体活检候选者。
