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鼻咽癌是头颈部常见的上皮来源的恶性肿瘤之一。18F-FDG PET/CT具有可提供全身显像的信息及反映病灶内部的代谢情况等优势,目前已被广泛应用于鼻咽癌的诊断。表皮生长因子受体(epidermal growth factor receptor,EGFR)属于内源性受体型酪氨酸激酶家族,EGFR 蛋白的过表达与头颈部恶性肿瘤的分化程度和增殖密切相关[1],EGFR高表达的恶性肿瘤通常意味着预后不良[2]。头颈部恶性肿瘤中EGFR的高表达会造成肿瘤细胞对放疗的抗性[3]。由于受到鼻咽癌发病部位的限制及其高度的放疗敏感性,放疗已成为治疗鼻咽癌的首选方式。以往有关于EGFR蛋白表达情况的临床检测主要以病理免疫组织化学法为主,但该方法属于有创性检查。Lee等[4]的研究结果表明,EGFR的表达水平与恶性肿瘤对18F-FDG摄取率的高低密切相关。本研究通过综合分析鼻咽癌患者的临床资料及18F-FDG PET/CT检查的相关代谢参数对EGFR表达水平的影响,探讨18F-FDG PET/CT检查是否可以作为评估鼻咽癌患者治疗前EGFR表达水平的影像学手段。
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61例鼻咽癌患者EGFR的表达情况:阴性4例、弱阳性23例、阳性18例、强阳性16例;EGFR低表达27例(低表达组)、高表达34例(高表达组);61例鼻咽癌患者EGFR阳性表达率为93%(57/61)。61例鼻咽癌患者肿瘤T分期情况:T1期8例、T2期20例、T3期18例、T4期15例。EGFR高表达组与EGFR低表达组的肿瘤T分期、肿瘤最大径之间的差异均有统计学意义(均P<0.05),而性别、年龄、病理分型之间的差异均无统计学意义(均 P>0.05)(表1)。
组别 男性/女性(例) 年龄( ±s,岁)$\bar x $ 肿瘤T分期(例) 病理分型(例) 肿瘤最大径(例) T1 T2 T3 T4 未分化型癌 鳞癌 分化型癌 <3 cm ≥3 cm EGFR低表达组(n=27) 18/9 51.33±12.01 6 12 7 2 13 12 2 19 8 EGFR高表达组(n=34) 26/8 50.38±13.51 2 8 11 13 21 9 4 14 20 检验值 χ2=0.720 t=−0.087 χ2=11.128 χ2=1.914 χ2=5.165 P值 0.396 0.931 0.010 0.384 0.023 注:EGFR为表皮生长因子受体 表 1 不同EGFR表达组的61例鼻咽癌患者的临床资料比较
Table 1. Comparison of clinical data of 61 nasopharyngeal carcinoma patients between different epidermal growth factor receptor expression groups
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61例鼻咽癌患者中,EGFR高表达组的SUVmax、MTV、TLG的中位数均明显高于EGFR低表达组,且差异均有统计学意义(均P<0.05)(表2)。
组别 SUVmax MTV(cm3) TLG EGFR低表达组(n=27) 7.80(7.40,13.60) 6.02(4.16,14.67) 50.80(16.35,82.23) EGFR高表达组(n=34) 11.50(12.90,21.21) 8.48(5.75,21.80) 131.89(32.83,241.23) U值 −4.197 −2.273 −2.425 P值 <0.01 0.023 0.015 注:EGFR为表皮生长因子受体;PET/CT为正电子发射断层显像计算机体层摄影技术;SUVmax为最大标准化摄取值;MTV为肿瘤代谢体积;TLG为肿瘤糖酵解总量 表 2 不同EGFR表达组的61例鼻咽癌患者的PET/CT代谢参数比较[ M(P25,P75)]
Table 2. PET/CT metabolism comparison of 61 nasopharyngeal carcinoma patients between different epidermal growth factor receptor expression groups [M(P25, P75)]
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单因素Logistic回归分析结果表明,肿瘤T分期、肿瘤最大径、SUVmax、MTV、TLG是EGFR表达水平的影响因素;当患者EGFR呈高表达时,肿瘤组织的SUVmax、MTV、TLG越高,其临床分期越晚,肿瘤体积越大(表3)。多因素Logistic分析结果显示,SUVmax(OR=1.340,95%CI:1.019~1.764,P=0.036)是预测 EGFR高表达的独立因素(表4)。
因素 OR值 95%CI P值 性别 1.625 0.527~5.011 0.398 年龄 0.994 0.995~1.035 0.771 肿瘤T分期 0.103 0.018~0.582 0.025 病理分型 未分化型癌 0.887 0.139~5.507 0.875 鳞癌 0.346 0.052~2.310 0.273 分化型癌 1.000 − − 肿瘤最大径 1.612 1.090~2.385 0.017 SUVmax 1.270 1.115~1.446 <0.01 MTV 1.008 1.002~1.014 0.015 TLG 1.085 1.015~1.160 0.016 注:EGFR为表皮生长因子受体;SUVmax为最大标准化摄取值;MTV为肿瘤代谢体积;TLG为肿瘤糖酵解总量;CI为置信区间。−表示无此项数据 表 3 61例鼻咽癌患者EGFR高表达的单因素Logistic回归 分析结果
Table 3. Univariate Logistic regression analysis of high expression of epidermal growth factor receptor in 61 patients with nasopharyngeal carcinoma
因素 OR值 95%CI P值 肿瘤T分期 0.489 0.056~4.298 0.519 肿瘤最大径 0.861 0.482~41.539 0.614 SUVmax 1.340 1.019~1.764 0.036 TLG 0.999 0.980~1.019 0.924 MTV 1.028 0.842~1.255 0.786 注:EGFR为表皮生长因子受体;SUVmax为最大标准化摄取值;TLG为肿瘤糖酵解总量;MTV为肿瘤代谢体积;CI为置信区间 表 4 61例鼻咽癌患者EGFR高表达的多因素Logistic回归 分析结果
Table 4. Multivariate Logistic regression analysis of high expression of epidermal growth factor receptor in 61 patients with nasopharyngeal carcinoma
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由图1可见,SUVmax预测EGFR高表达的最佳临界值为16.39(AUC=0.815,95%CI:0.709~0.921,P<0.01);MTV的最佳临界值为136.29 cm3(AUC=0.682,95%CI:0.548~0.816,P=0.015);TLG的最佳临界值为19.28(AUC=0.670,95%CI:0.535~0.805,P=0.023);SUVmax的诊断效能优于MTV和TLG。以上述SUVmax、MTV、TLG临界值诊断鼻咽癌的灵敏度分别为58.8%、50.0%、41.2%,特异度分别为96.3%、85.2%、96.3%。
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鼻咽癌EGFR高表达患者的SUVmax、MTV、TLG均高于低表达患者(图2、3),EGFR高表达患者肿瘤原发灶的侵犯范围较低表达患者更广。
鼻咽癌18F-FDG PET/CT 代谢参数与EGFR表达水平的相关性研究
Correlation study of 18F-FDG PET/CT metabolic parameters and EGFR expression level in nasopharyngeal carcinoma
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摘要:
目的 探讨18F-氟脱氧葡萄糖(FDG) PET/CT相关代谢参数预测鼻咽癌治疗前表皮生长因子受体(EGFR)表达水平的价值。 方法 回顾性分析2017年1月至2019年11月广西省柳州市工人医院收治的61例[男性44例、女性17例,年龄21~84(57.8±6.2)岁]经组织病理学检查确诊的鼻咽癌患者的临床资料及PET/CT显像资料。分析所有患者的18F-FDG PET/CT图像,计算最大标准化摄取值(SUVmax)、肿瘤代谢体积(MTV)、肿瘤糖酵解总量(TLG)。所有患者的肿瘤标本经链霉菌抗生物素蛋白-过氧化物酶连结(sp)法免疫组织化学染色法染色后,计算标本的EGFR阳性表达情况。采用χ2检验或Fisher确切概率法分析性别、肿瘤T分期、最大径、病理分型等计数资料;SUVmax、MTV、TLG两样本的组间比较采用Mann-Whitney U秩和检验;年龄的组间比较采用独立样本t检验。采用单因素Logistic回归方程分析临床病理因素、代谢参数等因素对EGFR表达水平的影响,把单因素分析中差异有统计学意义的因素纳入多因素Logistic回归分析模型中,评估EGFR表达水平的独立影响因素。绘制鼻咽癌患者代谢参数的受试者工作特征(ROC)曲线,评估其诊断效能。 结果 61例鼻咽癌患者的EGFR阳性表达率为93%(57/61),EGFR高表达34例(高表达组),EGFR低表达27例(低表达组)。EGFR高表达组的SUVmax、MTV、TLG明显高于低表达组(U=−4.197、−2.273、−2.425,均P<0.05)。EGFR高表达组与EGFR低表达组在肿瘤T分期、肿瘤最大径之间的差异均有统计学意义(χ2=11.128、5.165,均P<0.05),而在性别(χ2=0.720)、年龄(t=−0.087)、病理分型(χ2=1.914)之间的差异均无统计学意义(均P>0.05)。单因素回归分析结果显示,肿瘤T分期(OR=0.103,95%CI:0.018~0.582,P=0.025)、肿瘤最大径(OR=1.612,95%CI:1.090~2.385,P=0.017)、SUVmax(OR=1.270,95%CI:1.115~1.446,P<0.01)、MTV(OR=1.008,95%CI:1.002~1.014,P=0.015)、TLG(OR=1.085,95%CI:1.015~1.160,P=0.016)是EGFR表达水平的影响因素。多因素回归分析结果显示,SUVmax(OR=1.340,95%CI:1.019~1.764,P=0.036)是预测EGFR高表达的独立影响因素。ROC曲线结果表明,SUVmax[曲线下面积(AUC)=0.815,95%CI:0.709~0.921,P<0.01]对于预测EGFR高表达的诊断效能优于MTV(AUC=0.682,95%CI:0.548~0.816,P=0.015)、TLG(AUC=0.670,95%CI:0.535~0.805,P=0.023)。SUVmax、MTV、TLG临界值分别为16.39、136.29 cm3、19.28时诊断鼻咽癌的灵敏度分别为58.8%、50.0%、41.2%,特异度分别为96.3%、85.2%、96.3%。 结论 18F-FDG PET/CT代谢参数SUVmax可作为预测鼻咽癌患者EGFR表达水平的独立影响因素。 -
关键词:
- 鼻咽癌 /
- 氟脱氧葡萄糖F18 /
- 正电子发射断层显像术 /
- 体层摄影术,X线计算机 /
- 最大标准化摄取值 /
- 肿瘤代谢体积 /
- 糖酵解总量 /
- 表皮生长因子受体
Abstract:Objective To investigate the value of 18F-fluorodeoxyglucose (FDG) PET/CT related metabolic parameters in predicting epidermal growth factor receptor (EGFR) expression levels before the treatment of nasopharyngeal carcinoma (NPC). Methods The clinical and PET/CT imaging data of 61 patients (44 males and 17 females, aged 21–84 (57.8±6.2) years) with NPC that was diagnosed via hiopathological examination and who were admitted to the Nuclear Medicine Department of Guangxi Liuzhou Worker's Hospital from January 2017 to November 2019 were retrospectively analyzed. The 18F-FDG PET/CT images of all patients were analyzed to calculate the maximum standard uptake value (SUVmax), tumor metabolic volume (MTV), and total lesion glycolysis (TLG). The samples of all patients were subjected to streptavidin-perosidase immunohistochemical staining, and the positive expression of EGFR was calculated. Gender, T stage, pathological classification, maximum tumor diameter, and other enumeration data were analyzed through χ2 test or Fisher's exact probability. Mann–Whitney U test was adopted for the comparison of SUVmax, MTV, and TLG between two samples. Independent samples t test was applied for the comparison of ages between groups. Single factorial Logistic regression equation was used for the analysis of clinicopathological factors and metabolic parameters to evaluate the predictors of EGFR expression levels, and factors (P<0.05) with statistical significance in single factorial analysis were included in the multiple factorial Logistic regression analysis model to evaluate the independent predictors of EGFR expression levels. The receiver operator characteristic (ROC) curves of the three groups of the metabolic parameters of patients with NPC were drawn to evaluate diagnostic efficacy. Results The 61 NPC patients had positive EGFR expression rates of 93% (57/61). Among the patients, 34 had high EGFR expression levels and 27 had low EGFR expression levels. The SUVmax, MTV, and TLG of the high EGFR expression group were evidently higher than those of the low EGFR expression group (U=−4.197, −2.273, −2.425; all P<0.05). T stage and maximum tumor diameter were related to EGFR expression levels (χ2=11.128, 5.165; both P<0.05), whereas the difference in gender (χ2=0.720), age (t=−0.087), and pathological classification (χ2=1.914) between the high and low EGFR expression groups lacked statistical significance (all P>0.05). Single factorial regression analysis showed that patients with high T stage (OR=0.103, 95%CI: 0.018–0.582, P=0.025), maximum tumor diameter (OR=1.612, 95%CI: 1.090–2.385, P=0.017), SUVmax (OR=1.270, 95%CI: 1.115–1.446, P<0.01), MTV (OR=1.008, 95%CI: 1.002–1.014, P=0.015), and TLG (OR=1.085, 95%CI: 1.015–1.160, P=0.016) were likely to have high EGFR expression, and multiple factorial regression analysis indicated that SUVmax (OR=1.340, 95%CI: 1.019–1.764, P=0.036) was the independent predictor of high EGFR expression levels. The ROC curves indicated that the diagnostic efficacy of SUVmax (AUC=0.815, 95%CI: 0.709–0.921, P<0.01) in predicting high EGFR expression levels was obviously superior to that of MTV (AUC=0.682, 95%CI: 0.548–0.816, P=0.015) and TLG (AUC=0.670, 95%CI: 0.535–0.805, P=0.023). When the critital values of SUVmax, MTV and TLG were 16.39, 136.29 cm3, 19.28 respectively, the sensitivities were 58.8%, 50.0%, and 41.2%, respectively, and the specificities were 96.3%, 85.2%, and 96.3%, respectively. Conclusions The metabolic parameter SUVmax of 18F-FDG PET/CT can serve as the independent predictor of EGFR expression levels in patients with NPC. Moreover, 18F-FDG PET/CT examination can enable the noninvasive assessment of EGFR expression levels. -
表 1 不同EGFR表达组的61例鼻咽癌患者的临床资料比较
Table 1. Comparison of clinical data of 61 nasopharyngeal carcinoma patients between different epidermal growth factor receptor expression groups
组别 男性/女性(例) 年龄( ±s,岁)$\bar x $ 肿瘤T分期(例) 病理分型(例) 肿瘤最大径(例) T1 T2 T3 T4 未分化型癌 鳞癌 分化型癌 <3 cm ≥3 cm EGFR低表达组(n=27) 18/9 51.33±12.01 6 12 7 2 13 12 2 19 8 EGFR高表达组(n=34) 26/8 50.38±13.51 2 8 11 13 21 9 4 14 20 检验值 χ2=0.720 t=−0.087 χ2=11.128 χ2=1.914 χ2=5.165 P值 0.396 0.931 0.010 0.384 0.023 注:EGFR为表皮生长因子受体 表 2 不同EGFR表达组的61例鼻咽癌患者的PET/CT代谢参数比较[ M(P25,P75)]
Table 2. PET/CT metabolism comparison of 61 nasopharyngeal carcinoma patients between different epidermal growth factor receptor expression groups [M(P25, P75)]
组别 SUVmax MTV(cm3) TLG EGFR低表达组(n=27) 7.80(7.40,13.60) 6.02(4.16,14.67) 50.80(16.35,82.23) EGFR高表达组(n=34) 11.50(12.90,21.21) 8.48(5.75,21.80) 131.89(32.83,241.23) U值 −4.197 −2.273 −2.425 P值 <0.01 0.023 0.015 注:EGFR为表皮生长因子受体;PET/CT为正电子发射断层显像计算机体层摄影技术;SUVmax为最大标准化摄取值;MTV为肿瘤代谢体积;TLG为肿瘤糖酵解总量 表 3 61例鼻咽癌患者EGFR高表达的单因素Logistic回归 分析结果
Table 3. Univariate Logistic regression analysis of high expression of epidermal growth factor receptor in 61 patients with nasopharyngeal carcinoma
因素 OR值 95%CI P值 性别 1.625 0.527~5.011 0.398 年龄 0.994 0.995~1.035 0.771 肿瘤T分期 0.103 0.018~0.582 0.025 病理分型 未分化型癌 0.887 0.139~5.507 0.875 鳞癌 0.346 0.052~2.310 0.273 分化型癌 1.000 − − 肿瘤最大径 1.612 1.090~2.385 0.017 SUVmax 1.270 1.115~1.446 <0.01 MTV 1.008 1.002~1.014 0.015 TLG 1.085 1.015~1.160 0.016 注:EGFR为表皮生长因子受体;SUVmax为最大标准化摄取值;MTV为肿瘤代谢体积;TLG为肿瘤糖酵解总量;CI为置信区间。−表示无此项数据 表 4 61例鼻咽癌患者EGFR高表达的多因素Logistic回归 分析结果
Table 4. Multivariate Logistic regression analysis of high expression of epidermal growth factor receptor in 61 patients with nasopharyngeal carcinoma
因素 OR值 95%CI P值 肿瘤T分期 0.489 0.056~4.298 0.519 肿瘤最大径 0.861 0.482~41.539 0.614 SUVmax 1.340 1.019~1.764 0.036 TLG 0.999 0.980~1.019 0.924 MTV 1.028 0.842~1.255 0.786 注:EGFR为表皮生长因子受体;SUVmax为最大标准化摄取值;TLG为肿瘤糖酵解总量;MTV为肿瘤代谢体积;CI为置信区间 -
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