Division of Thoracic Oncology, Shizuoka Cancer Center, Japan.
Division of Thoracic Surgery, Shizuoka Cancer Center, Japan.
Lung Cancer. 2019 Feb;128:152-157. doi: 10.1016/j.lungcan.2018.12.005. Epub 2018 Dec 5.
This study assessed the associations between the molecular signatures and clinical information in non-small cell lung cancer (NSCLC) patients with postoperative disease-free survival (p-dfs) to identify novel prognostic factors, focusing on associations with driver gene alterations.
Between February 2014 and September 2015, 242 patients with NSCLC, including 192 patients with adenocarcinoma (Ad) and 50 patients with squamous cell carcinoma (Sq), underwent surgery and were enrolled in this study. Surgically resected tissues were subjected to whole exome sequencing. Mt detected in 138 cancer-related genes were evaluated as driver mutations. A multivariate analysis using the multi-state model was used to establish the associations between co-variables and p-dfs.
Postoperative recurrence (p-rec) was observed in 49 (20.2%) and 19 (7.9%) patients with Ad and Sq, respectively. The median (range) follow-up period for all the censored cases was 2.5 (2.0-3.5) years. The characteristics of the patients with postoperative recurrence were as follows: median age (range), 71 (50-87) years; male, 38 (56%); smoker, 51 (75%); p-stage (I/II/III), 30 (44%)/19 (28%)/19 (28%); histological type (Ad/Sq), 49 (72%)/19 (28%); adjuvant chemotherapy (yes/no), 30 (44%)/38 (56%); and driver gene alteration (presence/absence), 65 (96%)/3 (4%). In univariate analyses, age (<70/≧70 years), smoking history (yes/no), p-stage (I, II/III), histological type (Ad/Sq), and driver mutation (presence/absence) were favorable prognostic factors (P = .017, P = .048, P = .0002, P = .006, P = .029, respectively). A multivariate analysis also revealed a significant association between the driver mutation status and p-dfs (P = .046; odds ratio [OR], 2.86; 95% confidence interval [CI], 1.02-8.08), when adjusted according to histological type (P = .10), smoking status (P = .09), gender (P = .51), age (P = .008) and p-stage (P = .00003).
The driver mutation status may be an independent prognostic factor of p-dfs in NSCLC.
本研究旨在评估非小细胞肺癌（NSCLC）患者术后无病生存（p-dfs）的分子特征与临床信息之间的相关性，以确定新的预后因素，重点关注与驱动基因突变的相关性。
2014 年 2 月至 2015 年 9 月，共纳入 242 例接受手术治疗的 NSCLC 患者，其中腺癌（Ad）患者 192 例，鳞癌（Sq）患者 50 例。对手术切除的组织进行全外显子测序。评估了 138 个与癌症相关基因中的 Mt 检测到的驱动突变。采用多状态模型的多变量分析来建立协变量与 p-dfs 之间的关联。
Ad 和 Sq 患者术后复发（p-rec）分别为 49（20.2%）和 19（7.9%）例。所有截尾病例的中位（范围）随访时间为 2.5（2.0-3.5）年。术后复发患者的特征如下：中位年龄（范围），71（50-87）岁；男性，38（56%）；吸烟者，51（75%）；p 期（I/II/III），30（44%）/19（28%）/19（28%）；组织学类型（Ad/Sq），49（72%）/19（28%）；辅助化疗（是/否），30（44%）/38（56%）；和驱动基因突变（存在/缺失），65（96%）/3（4%）。单因素分析显示，年龄（<70/≧70 岁）、吸烟史（是/否）、p 期（I、II/III）、组织学类型（Ad/Sq）和驱动基因突变（存在/缺失）为预后良好的因素（P=0.017，P=0.048，P=0.0002，P=0.006，P=0.029）。多因素分析也显示，驱动基因突变状态与 p-dfs 显著相关（P=0.046；优势比[OR]，2.86；95%置信区间[CI]，1.02-8.08），当根据组织学类型（P=0.10）、吸烟状况（P=0.09）、性别（P=0.51）、年龄（P=0.008）和 p 期（P=0.00003）进行调整时。
驱动基因突变状态可能是非小细胞肺癌患者 p-dfs 的一个独立预后因素。
