Precision Medicine Lung Cancer Center, Konkuk University Medical Center, Seoul, Republic of Korea.
Department of Pulmonary Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea.
Ann Surg Oncol. 2021 Jul;28(7):3983-3993. doi: 10.1245/s10434-020-09276-x. Epub 2020 Nov 2.
Despite surgical resection, early lung adenocarcinoma has a recurrence rate of 20-50%. No clear predictive markers for recurrence of early lung adenocarcinoma are available. Targeted next-generation sequencing (NGS) is rarely used to identify recurrence-related genes. We aimed to identify genetic alterations that can predict recurrence, by comparing the molecular profiles of patient groups with and without recurrence.
Tissues from 230 patients with resected stage I-II lung adenocarcinoma (median follow-up: 49 months) were analyzed via targeted NGS for 207 cancer-related genes. The recurrence-free survival according to the number and type of mutation was estimated using the Kaplan-Meier method. Independent predictive biomarkers related to recurrence were identified using the Cox proportional hazards model.
Recurrence was observed in 64 patients (27.8%). In multivariate analysis adjusted for age, sex, smoking history, stage, surgical mode, and visceral pleural invasion, the CTNNB1 mutation and fusion genes (ALK, ROS1, RET) were negative prognostic factors for recurrence in early-stage lung adenocarcinoma (HR 4.47, p = 0.001; HR 2.73, p = 0.009). EGFR mutation was a favorable factor (HR 0.51, p = 0.016), but the CTNNB1/EGFR co-mutations were negative predictors (HR 19.2, p < 0.001). TP53 mutation was a negative predictor compared with EGFR mutation for recurrence (HR 5.24, p = 0.02).
Targeted NGS can provide valuable information to predict recurrence and identify patients at high recurrence risk, facilitating selection of the treatment strategy among close monitoring and adjuvant-targeted therapy. Larger datasets are required to validate these findings.
尽管进行了手术切除，早期肺腺癌仍有 20-50%的复发率。目前尚无明确的早期肺腺癌复发预测标志物。靶向下一代测序（NGS）很少用于识别与复发相关的基因。我们旨在通过比较有和无复发患者组的分子谱，来确定可预测复发的遗传改变。
对 230 例接受 I-II 期肺腺癌切除治疗的患者（中位随访时间：49 个月）的组织进行靶向 NGS 分析，检测 207 个与癌症相关的基因。采用 Kaplan-Meier 法估计无复发生存率，根据突变数量和类型进行分组。采用 Cox 比例风险模型确定与复发相关的独立预测生物标志物。
64 例患者（27.8%）出现复发。在多变量分析中，校正年龄、性别、吸烟史、分期、手术方式和脏层胸膜侵犯后，CTNNB1 突变和融合基因（ALK、ROS1、RET）是早期肺腺癌复发的不良预后因素（HR 4.47，p=0.001；HR 2.73，p=0.009）。EGFR 突变是有利因素（HR 0.51，p=0.016），但 CTNNB1/EGFR 共突变是不良预测因素（HR 19.2，p<0.001）。与 EGFR 突变相比，TP53 突变是复发的不良预测因素（HR 5.24，p=0.02）。
靶向 NGS 可提供有价值的信息来预测复发，识别高复发风险的患者，有助于在密切监测和辅助靶向治疗之间选择治疗策略。需要更大的数据集来验证这些发现。
