Detection of oncogenic mutations in resected bronchial margins by next-generation sequencing indicates early relapse in stage IA lung adenocarcinoma patients.
Detection of oncogenic mutations in resected bronchial margins by next-generation sequencing indicates early relapse in stage IA lung adenocarcinoma patients.
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通过下一代测序检测切除的支气管边缘的致癌突变表明 IA 期肺腺癌患者出现早期复发
DOI：
10.18632/oncotarget.16539
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发表时间：
2017-06-20
期刊：
影响因子：
--
通讯作者：
Song Y
中科院分区：
文献类型：
--
作者：
Lv T;Zou J;Liu H;Shen Q;Lu Z;Zhou X;Wang X;Song Y
I期非小细胞肺癌（NSCLC）患者的复发率相对较高，约为30-35%。我们假设这种复发风险升高是由于常规光学显微镜未检测到支气管边缘肿瘤细胞的存在。本研究纳入临床分期为IA期（T1N0M0） NSCLC患者，其中早期复发（ER）患者8例，无复发（NR）患者6例。收集原发肿瘤、支气管边缘和正常肺组织并送到中心位置进行靶向下一代测序分析。所有患者均为肺腺癌。所有肿瘤组织样本中均发现基因突变（100%）。87.5%（7/8）的早期复发患者的支气管边缘组织发现了致癌基因突变，而只有16.7%（1/6）的边缘组织未复发（NR）患者发现了基因突变。此外，原发性肿瘤与支气管边缘的一致性相对较高，8例ER患者中有4例（50%）至少有一个相同的突变。此外，根据边缘组织的基因突变情况，87.5%（7/8）的支气管边缘至少有一个基因突变的患者有局部复发或转移，而未检测到任何突变的患者只有16.7%（1/6）有复发迹象，复发率显著高于边缘阴性突变组（p (log-rank) = 0.023）。在早期NSCLC患者中，支气管边缘存在癌性突变可能代表着肿瘤的隐匿性残留和复发风险的增加。因此，评估支气管边缘的分子状态可能有助于确定可能从广泛手术或辅助治疗中获益的患者。
Stage I non-small cell lung cancer (NSCLC) patients experience a relatively high rate of recurrence, ranging from about 30-35%. We hypothesized that this elevated risk of recurrence is due to the presence of tumor cells at bronchial margins which was undetected by conventional light microscopy. Patients with clinical stage IA (T1N0M0) NSCLC were enrolled in this study, which included 8 early-relapse(ER) and 6 no-relapse(NR) patients. Primary tumor, bronchial margin, and normal lung tissues were collected and sent to a central site for targeted next-generation sequencing analysis. All of the patients were lung adenocarcinoma. Gene mutations were identified in all tumor tissue samples (100%). Oncogenic mutations were identified in 87.5%(7/8) bronchial margins of early relapse patients, whereas only 16.7%(1/6) no-relapse (NR) patient of marginal tissue had identified gene mutation. Additionally, concordance between primary tumor and bronchial margins was relatively high, with 4 of 8 (50%) ER patients having at least one identical mutation. Moreover, according to the gene mutation status in marginal tissue, 87.5% (7/8) of patients with at least one gene mutation in the bronchial margins had local recurrence or metastasis, whereas only 16.7% (1/6) of patients without any mutation detected had signs of relapse, the recurrence rate was significantly higher than that of the negative mutation margin group ((p (log-rank) = 0.023). The existence of oncogenic mutations in bronchial margins may represent occult residual tumor and elevated risk of recurrence in early stage NSCLC patients. Thus, assessing molecular status in bronchial margins may help identify patients who might benefit from extensive surgery or adjuvant treatment.
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