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肺癌是目前全世界范围内发病率和病死率位居前列的肿瘤[1],非小细胞肺癌(non-small cell lung cancer,NSCLC)是其最常见的类型[2]。Kim等[3]的研究结果显示,部分肺癌患者可发生表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变,对于EGFR基因突变的NSCLC患者,EGFR酪氨酸激酶抑制剂能够提高患者疗效、降低复发率、延长总生存期[3]。近年来,肺癌突变基因与影像特征之间的关系成为研究的热点[4],国内外针对肺癌EGFR基因突变与影像特征相关性研究的对象大多为Ⅲ ~Ⅳ期患者,检测标本来源于穿刺或手术,结论尚未统一。本研究探讨Ⅰ ~ⅢB期可切除周围型NSCLC患者EGFR基因突变与临床及高分辨率CT(high resolution CT,HRCT)影像特征的相关性,旨在为肺癌的精准治疗提供影像学依据。
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在164例Ⅰ~ⅢB期周围型NSCLC患者中,EGFR基因突变型组114例(69.51%)、野生型组50例(30.49%)。与EGFR野生型组相比,EGFR基因突变型组多见于女性、年龄<60岁、无吸烟史及病理类型为肺腺癌的患者,且2组间差异均有统计学意义(均P<0.05)。2组患者的其他临床特征见表1。
临床特征 基因突变型组
(n=114)基因野生型组
(n=50)χ2值 P值 性别 21.91 <0.001 男性 46(40.4) 40(80.0) 女性 68(59.6) 10(20.0) 年龄 −4.71 <0.001 ≥60岁 52(45.6) 36(72.0) <60岁 62(54.4) 14(28.0) 吸烟史 34.64 <0.001 有 20(17.5) 32(64.0) 无 94(82.5) 18(36.0) 癌胚抗原水平 1.49 0.223 升高 28(24.6) 8(16.0) 正常 86(75.4) 42(84.0) 术后临床分期 0.96 0.617 Ⅰ期 78(68.4) 38(76.0) Ⅱ期 6(5.3) 2(4.0) ⅢA~ⅢB期 30(26.3) 10(20.0) 病理类型 − <0.001 鳞癌和(或)腺鳞癌 4(3.5) 18(36.0) 腺癌 110(96.5) 32(64.0) 注:−表示Fisher确切概率检验,无检验值;EGFR为表皮生长因子受体 表 1 164例周围型非小细胞肺癌患者的临床特征与EGFR 基因突变的关系[例(%)]
Table 1. Relationship between clinical features and epidermal growth factor receptor gene mutation in 164 patients with peripheral non-small cell lung cancer (cases (%))
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由表2可知,与EGFR野生型组相比,EGFR基因突变型组患者的肿瘤最大径小于野生型组患者[(2.52±1.51)cm对(4.12±6.07)cm],且肿瘤多位于右肺,密度类型多为GGO和(或)mGGO,多伴有分叶征、支气管充气征和胸膜牵拉征,2组的差异均有统计学意义(t=2.14,χ2=10.13~19.05,均P<0.05)。而2组在肿瘤毛刺征、空泡征、空洞征、坏死、血管集束征和胸腔淋巴结肿大等征象中的差异均无统计学意义(均P>0.05)。EGFR基因突变型组与野生型组患者的典型CT图见图1。
图 1 3例周围型非小细胞肺癌EGFR基因突变型与野生型患者的典型CT图
Figure 1. CT images of patients with epidermal growth factor receptor gene mutation and wild-type gene in 3 cases of peripheral non-small cell lung cancer
影像特征 基因突变型
组(n=114)基因野生型
组(n=50)检验值 P值 肿瘤大小(cm, )$\bar x\pm s $ 2.52±1.51 4.12±6.07 t=2.14 0.036 肿瘤部位[例(%)] χ2=10.13 0.001 左肺 34(29.8) 28(56.0) 右肺 80(70.2) 22(44.0) 密度类型[例(%)] χ2=19.05 <0.001 实性 40(35.1) 36(72.0) GGO和(或)mGGO 74(64.9) 14(28.0) 分叶征[例(%)] χ2=15.00 <0.001 有 96(84.2) 28(56.0) 无 18(15.8) 22(44.0) 毛刺征[例(%)] χ2=0.83 0.362 有 68(59.6) 26(52.0) 无 46(40.4) 24(48.0) 空泡征[例(%)] χ2=0.41 0.524 有 28(24.6) 10(20.0) 无 86(75.4) 40(80.0) 空洞征[例(%)] − 1.000 有 4(3.5) 2(3.6) 无 110(96.5) 48(96.4) 血管集束征[例(%)] χ2=0.40 0.527 有 18(15.8) 6(10.7) 无 96(84.2) 44(89.3) 支气管充气征[例(%)] χ2=16.69 <0.001 有 62(54.4) 10(20.0) 无 52(45.6) 40(80.0) 坏死[例(%)] χ2=2.33 0.127 有 6(5.3) 6(12.0) 无 108(94.7) 44(88.0) 胸膜牵拉征[例(%)] χ2=10.80 0.001 有 92(80.7) 28(56.0) 无 22(19.3) 22(44.0) 胸腔淋巴结肿大[例(%)] χ2=0.98 0.322 有 26(22.8) 8(25.0) 无 88(77.2) 42(75.0) 注:−表示Fisher确切概率检验,无检验值;CT为计算机体层摄影术;EGFR为表皮生长因子受体;GGO为磨玻璃影;mGGO为混合磨玻璃影 表 2 164例周围型非小细胞肺癌患者的高分辨率CT影像 特征与EGFR基因突变的关系
Table 2. Relationship between high resolution CT imaging features and epidermal growth factor receptor gene mutation in 164 patients with peripheral non-small cell lung cancer
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将单因素分析中差异有统计学意义的变量进一步纳入二元Logistic回归模型,结果显示,患者无吸烟史和肿瘤伴有分叶征是周围型NSCLC患者EGFR基因突变的独立预测因子(表3)。ROC曲线分析结果显示,回归模型的AUC为0.858(图2)。
影响因素 B值 SE值 Wald值 OR值 95%置信区间 P值 性别 −0.486 0.644 0.569 0.615 0.174~2.175 0.451 年龄 −0.469 0.516 0.826 0.625 0.227~1.720 0.363 吸烟 −1.492 0.624 5.719 0.225 0.066~0.764 <0.05 病理类型 1.185 0.784 2.285 2.548 0.704~15.213 0.131 肿瘤部位 0.935 0.482 3.768 2.548 0.991~6.549 0.052 肿瘤大小 −0.135 0.078 2.979 0.874 0.750~1.018 0.052 密度类型 −0.074 0.632 0.014 0.928 0.269~3.207 0.906 分叶征 1.207 0.577 4.377 3.344 1.079~10.360 <0.05 支气管充气征 0.865 0.611 2.005 2.375 0.717~7.864 0.157 胸膜牵拉征 0.116 0.547 0.045 1.123 0.385~3.278 0.832 注:EGFR为表皮生长因子受体;SE为标准误差;OR为比值比 表 3 164例周围型非小细胞肺癌患者EGFR基因突变相关 变量的Logistic回归分析结果
Table 3. Logistic regression analysis results of factors related to epidermal growth factor receptor gene mutation in 164 patients with peripheral non-small cell lung cancer
Ⅰ ~ⅢB期可切除周围型非小细胞肺癌患者临床及高分辨率CT影像特征与EGFR基因突变的相关性研究
Correlation between clinical and HRCT imaging features with epidermal growth factor receptor gene mutation in patients with stage Ⅰ −ⅢB resectable peripheral non-small cell lung cancer
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摘要:
目的 探讨Ⅰ ~ⅢB期可切除周围型非小细胞肺癌(NSCLC)患者的临床及高分辨率CT(HRCT)影像特征与表皮生长因子受体(EGFR)基因突变的相关性。 方法 回顾性分析2019年1月至2021年4月于惠州市中心人民医院行手术切除、术后行EGFR基因检测且临床分期为Ⅰ ~ⅢB期的周围型NSCLC患者164例,其中男性86例、女性78例,年龄(60.3±9.3)岁。根据EGFR基因检测结果将患者分为EGFR基因突变型组和野生型组,分析患者的临床及HRCT影像特征并进行统计学分析。计量资料的比较采用两独立样本t检验,计数资料的比较采用χ2检验或Fisher确切概率检验。筛选差异有统计学意义的指标纳入二元Logistic 回归分析。采用受试者工作特征(ROC)曲线的曲线下面积对构建的回归模型的诊断效能进行评估。 结果 164例NSCLC患者中,EGFR基因突变型组114例(69.51%)、野生型组50例(30.49%)。与EGFR野生型组比较,EGFR基因突变型组多见于女性、年龄<60岁、无吸烟史、病理类型为肺腺癌的患者,且2组间的差异均有统计学意义(χ2=21.91、−4.71、34.64,Fisher确切概率法,均P<0.05)。HRCT影像特征中,EGFR基因突变型组肿瘤最大径小于野生型组[(2.52±1.51) cm对(4.12±6.07) cm],且肿瘤多位于右肺,密度类型多为磨玻璃影和(或)混合磨玻璃影,多伴有分叶征、支气管充气征和胸膜牵拉征,与EGFR野生型组相比,差异均有统计学意义(t=2.14,χ2=10.13~19.05,均P<0.05)。2组患者在术后临床分期、癌胚抗原水平、肿瘤伴有毛刺征、坏死、血管集束征、空泡征、空洞征、胸腔淋巴结肿大中的差异均无统计学意义(χ2=0.40~2.33,Fisher确切概率法,均P>0.05)。Logistic回归分析结果显示,患者无吸烟史(OR=0.225,95%CI:0.066~0.764)和肿瘤伴有分叶征(OR=3.344,95%CI:1.079~10.360)是EGFR基因突变的独立预测因子(均P<0.05),回归模型的ROC曲线的曲线下面积为0.858。 结论 Ⅰ ~ⅢB期可切除周围型NSCLC的临床及HRCT影像特征与EGFR基因突变具有一定的相关性,对指导临床评估患者情况有重要意义。 -
关键词:
- 癌,非小细胞肺 /
- 体层摄影术,X线计算机 /
- 表皮生长因子受体 /
- 基因突变
Abstract:Objective To investigate the correlation between epidermal growth factor receptor (EGFR) gene mutation with clinical and high-resolution CT (HRCT) imaging features in patients with stages Ⅰ −ⅢB resectable peripheral non-small cell lung cancer (NSCLC). Methods A total of 164 patients with peripheral NSCLC who underwent lung cancer resection, EGFR genetic testing, and clinical staging of Ⅰ −ⅢB in Huizhou Central People's Hospital from January 2019 to April 2021 were retrospectively analyzed. The cohort included 86 males and 78 females, aged 60.3±9.3 years. According to the results of EGFR genetic testing, the patients were divided into EGFR mutation and wild-type groups. The clinical and HRCT imaging features of the patients were analyzed and statistically analyzed. The measurement data were compared by two-independent-sample t-test, and the counting data were compared by chi-square and Fisher's exact probability tests. Indicators with statistical differences were selected for binary Logistic regression analysis. The area under curve of the receiver operating characteristic (ROC) curve was used in evaluating the diagnostic efficiency of the regression model. Results Among the 164 patients with NSCLC, 114 (69.51%) were confirmed to have EGFR mutations, and 50 (30.49%) had wild-type EGFR. Compared with the wild-type EGFR, EGFR mutations were more frequent in non smoking, female patients aged <60 years with a pathological type of adenocarcinoma. Differences between the groups were statistically significant (χ2=21.91, −4.71, 34.64; Fisher's exact probability method, all P<0.05). As observed in HRCT imaging features, the maximum diameter of EGFR mutation group was smaller than that of the wild-type group ((2.52±1.51) cm vs. (4.12±6.07) cm), and the tumors were mostly located in the right lung, with ground-glass opacity or mixed ground-glass opacity, lobulation sign, bronchial inflation sign, and pleural traction sign, compared with the wild-type group, and the differences were statistically significant (t=2.14, χ2=10.13–19.05, all P<0.05). No significant differences in postoperative clinical stage, carcinoembryonic antigen level, lesions with burr signs, necrosis, vascular convergence sign, vacuole sign, cavity sign and thoracic lymphadenopathy were found between the groups (χ2=0.40–2.33, Fisher's exact probability method, all P>0.05). The results of Logistic regression analysis showed that patients with no smoking history (OR=0.225, 95%CI: 0.066–0.764) and tumor accompanied by lobulation sign (OR=3.344, 95%CI: 1.079–10.360) are the independent predictors of EGFR gene mutation (all P<0.05), and the area under the curve of the regression model was 0.858. Conclusion The clinical and imaging features of resectable peripheral NSCLC in stages Ⅰ −ⅢB are correlated with EGFR gene mutation, which are of great significance to assess the patient's condition. -
表 1 164例周围型非小细胞肺癌患者的临床特征与EGFR 基因突变的关系[例(%)]
Table 1. Relationship between clinical features and epidermal growth factor receptor gene mutation in 164 patients with peripheral non-small cell lung cancer (cases (%))
临床特征 基因突变型组
(n=114)基因野生型组
(n=50)χ2值 P值 性别 21.91 <0.001 男性 46(40.4) 40(80.0) 女性 68(59.6) 10(20.0) 年龄 −4.71 <0.001 ≥60岁 52(45.6) 36(72.0) <60岁 62(54.4) 14(28.0) 吸烟史 34.64 <0.001 有 20(17.5) 32(64.0) 无 94(82.5) 18(36.0) 癌胚抗原水平 1.49 0.223 升高 28(24.6) 8(16.0) 正常 86(75.4) 42(84.0) 术后临床分期 0.96 0.617 Ⅰ期 78(68.4) 38(76.0) Ⅱ期 6(5.3) 2(4.0) ⅢA~ⅢB期 30(26.3) 10(20.0) 病理类型 − <0.001 鳞癌和(或)腺鳞癌 4(3.5) 18(36.0) 腺癌 110(96.5) 32(64.0) 注:−表示Fisher确切概率检验,无检验值;EGFR为表皮生长因子受体 表 2 164例周围型非小细胞肺癌患者的高分辨率CT影像 特征与EGFR基因突变的关系
Table 2. Relationship between high resolution CT imaging features and epidermal growth factor receptor gene mutation in 164 patients with peripheral non-small cell lung cancer
影像特征 基因突变型
组(n=114)基因野生型
组(n=50)检验值 P值 肿瘤大小(cm, )$\bar x\pm s $ 2.52±1.51 4.12±6.07 t=2.14 0.036 肿瘤部位[例(%)] χ2=10.13 0.001 左肺 34(29.8) 28(56.0) 右肺 80(70.2) 22(44.0) 密度类型[例(%)] χ2=19.05 <0.001 实性 40(35.1) 36(72.0) GGO和(或)mGGO 74(64.9) 14(28.0) 分叶征[例(%)] χ2=15.00 <0.001 有 96(84.2) 28(56.0) 无 18(15.8) 22(44.0) 毛刺征[例(%)] χ2=0.83 0.362 有 68(59.6) 26(52.0) 无 46(40.4) 24(48.0) 空泡征[例(%)] χ2=0.41 0.524 有 28(24.6) 10(20.0) 无 86(75.4) 40(80.0) 空洞征[例(%)] − 1.000 有 4(3.5) 2(3.6) 无 110(96.5) 48(96.4) 血管集束征[例(%)] χ2=0.40 0.527 有 18(15.8) 6(10.7) 无 96(84.2) 44(89.3) 支气管充气征[例(%)] χ2=16.69 <0.001 有 62(54.4) 10(20.0) 无 52(45.6) 40(80.0) 坏死[例(%)] χ2=2.33 0.127 有 6(5.3) 6(12.0) 无 108(94.7) 44(88.0) 胸膜牵拉征[例(%)] χ2=10.80 0.001 有 92(80.7) 28(56.0) 无 22(19.3) 22(44.0) 胸腔淋巴结肿大[例(%)] χ2=0.98 0.322 有 26(22.8) 8(25.0) 无 88(77.2) 42(75.0) 注:−表示Fisher确切概率检验,无检验值;CT为计算机体层摄影术;EGFR为表皮生长因子受体;GGO为磨玻璃影;mGGO为混合磨玻璃影 表 3 164例周围型非小细胞肺癌患者EGFR基因突变相关 变量的Logistic回归分析结果
Table 3. Logistic regression analysis results of factors related to epidermal growth factor receptor gene mutation in 164 patients with peripheral non-small cell lung cancer
影响因素 B值 SE值 Wald值 OR值 95%置信区间 P值 性别 −0.486 0.644 0.569 0.615 0.174~2.175 0.451 年龄 −0.469 0.516 0.826 0.625 0.227~1.720 0.363 吸烟 −1.492 0.624 5.719 0.225 0.066~0.764 <0.05 病理类型 1.185 0.784 2.285 2.548 0.704~15.213 0.131 肿瘤部位 0.935 0.482 3.768 2.548 0.991~6.549 0.052 肿瘤大小 −0.135 0.078 2.979 0.874 0.750~1.018 0.052 密度类型 −0.074 0.632 0.014 0.928 0.269~3.207 0.906 分叶征 1.207 0.577 4.377 3.344 1.079~10.360 <0.05 支气管充气征 0.865 0.611 2.005 2.375 0.717~7.864 0.157 胸膜牵拉征 0.116 0.547 0.045 1.123 0.385~3.278 0.832 注:EGFR为表皮生长因子受体;SE为标准误差;OR为比值比 -
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