18F?FDG PET/CT代谢参数预测胃癌原发灶HER2低表达状态
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南京医科大学第一附属医院核医学科

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国家卫生健康委核医学重点实验室项目;江苏省分子核医学重点实验室(KF202206)


Predicting the HER2 Low Expression Status in Primary Gastric Cancer Lesions Using 18F?FDG PET/CT-Derived Metabolic Parameters
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Department of Nuclear Medicine,the First Affiliated Hospital of Nanjing Medical University

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    摘要:

    目的:探讨基线18氟-氟代脱氧葡萄糖正电子发射计算机断层扫描(18F-fluorodeoxyglucose positron emission tomography/computed tomography, 18F-FDG PET/CT)相关代谢参数对疗前胃癌原发灶人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)低表达状态的预测价值。方法:回顾性分析治疗前行18F-FDG PET/CT检查的110例胃腺癌患者的临床病理及18F-FDG PET影像资料。其中HER2缺失表达 35例,低表达46例,高表达29例。采用Kruskal-Wallis H检验和χ²检验进行三组间临床特征及PET代谢参数比较并进行事后两两比较(两两比较参考Bonferroni法校正的检验水准)。采用LASSO-Logistic回归分析法筛选出预测胃癌原发灶HER2低表达的影响因素并构建预测模型。 采用Bootstrap法(重复抽样1000次)进行内部验证。绘制受试者工作特征(receiver operating characteristic,ROC)曲线并计算曲线下面积(area under the curve,AUC)以评估模型的预测效能。校准曲线和临床决策曲线分析(decision?curve?analysis,DCA)用于评估模型的校准度及临床效用。结果:在临床特征方面,分化程度及癌胚抗原(carcinoembryonic antigen,CEA)水平在HER2低表达组与HER2缺失表达组间差异有统计学意义(P<0.05)。远处转移、印戒成分及CEA水平在HER2低表达组与HER2 高表达组间差异有统计学意义(P<0.05)。在PET/CT代谢参数方面,除40%阈值下的最小标准摄取值(minimum standardized uptake value,SUVmin),其余参数在HER2低表达组与非HER2低表达组间差异均具有统计学意义(P<0.05)。LASSO-Logistic回归分析显示分化程度、CEA水平、原发灶长径、40%及80%阈值下的病灶糖酵解总量(total lesion glycolysis,TLG)是HER2低表达的影响因素。因TLG40%与TLG80%可能存在共线性,故分别与其余3个参数构建LASSO-Logistic回归预测模型1及模型2。模型1的 AUC为0.668 (95% CI: 0.559-0.752),灵敏度为87.0%,特异度为42.2%;模型2的AUC为0.723 (95% CI: 0.630-0.804),灵敏度为65.2%,特异度为76.6%。校准曲线和DCA显示两模型均具有较好的校准度及临床净获益。其中模型1中TLG 40%[OR=0.983 (95% CI:0.970~0.996), P=0.011] 为HER2低表达的独立影响因素,AUC为0.387 (95% CI: 0.283~0.491);模型2中TLG 80%[OR=0.726 (95% CI:0.586~0.898), P=0.003] 为HER2低表达的独立影响因素,AUC为0.510 (95% CI: 0.399~0.622)。结论:18F-FDG PET代谢参数可无创预测胃癌原发灶HER2低表达状态,联合临床参数预测效能更佳,有望应用于临床。

    Abstract:

    Objective: To investigate the predictive value of baseline 18F-fluorodeoxyglucose positron emission tomography/computed tomography(18F-FDG PET/CT)derived metabolic parameters in assessing low expression status of human epidermal growth factor receptor 2(HER2)in primary gastric cancer lesions prior to treatment. Methods: We retrospectively analyzed the clinicopathological data and 18F-FDG PET findings from 110 patients with gastric adenocarcinoma who underwent 18F-FDG PET/CT examination before treatment. Among them, 35 exhibited HER2 absent expression, 46 demonstrated HER2 low expression, and 29 showed HER2 high expression. The Kruskal–Wallis H test and chi-square test were used to compare clinical characteristics and PET metabolic parameters among the three groups, followed by post-hoc pairwise comparisons(with Bonferroni correction for the significance level). LASSO-Logistic regression analysis was adopted to screen the influencing factors predicting HER2 low expression in primary gastric cancer lesions and construct the predictive models. Employ the Bootstrap method(involving 1,000 repeated samplings)for internal validation. Plot the receiver operating characteristic(ROC)curve and compute the area under the curve(AUC)to assess the predictive values of each model. Calibration curves and decision curve analysis(DCA)were adopted to assess the calibration and clinical utility of the models. Results: In terms of clinical characteristics, there were statistically significant differences in the degree of differentiation and carcinoembryonic antigen(CEA)levels between the HER2 low expression group and the HER2 absent expression group(P<0.05). There were also statistically significant differences in distant metastasis, signet-ring component, and CEA levels between the HER2 low expression group and the HER2 high expression group(P<0.05). In terms of PET/CT metabolic parameters, except for the minimum standardized uptake value(SUVmin)at the 40% threshold, all other parameters showed statistically significant differences between the HER2 low expression group and the non-HER2 low expression group(P<0.05). LASSO-Logistic regression analysis revealed that degree of differentiation, CEA level, maximum diameter of primary lesion, 40% and 80% total lesion glycolysis(TLG)were influencing factors for HER2 low expression. Given the potential multicollinearity between TLG 40% and TLG 80%, two LASSO Logistic regression predictive models(Model 1 and Model 2)were separately constructed by incorporating each of the two indicators together with the other three parameters. Model 1 yielded an AUC of 0.668(95% CI: 0.559–0.752, with a sensitivity of 87.0% and a specificity of 42.2%; Model 2 achieved an AUC of 0.723(95% CI: 0.630–0.804), with a sensitivity of 65.2% and a specificity of 76.6%. Calibration curves and decision curve analysis(DCA)demonstrated that both models exhibited favorable calibration and satisfactory clinical net benefit. In Model 1, TLG40% was an independent influencing factor for HER2 low expression, with an OR of 0.983(95% CI: 0.970–0.996, P= 0.011)and an AUC of 0.387(95% CI: 0.283–0.491). In Model 2, TLG80% served as an independent influencing factor for HER2 low expression, with an OR of 0.726(95% CI: 0.586–0.898, P=0.003)and an AUC of 0.510(95% CI: 0.399–0.622). Conclusion: 18F-FDG PET related metabolic parameters can noninvasively predict the HER2 low expression status in gastric cancer, and the combination with clinical parameters achieves optimal predictive performance, which is promising for clinical application.

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  • 收稿日期:2026-07-08
  • 最后修改日期:2026-09-11
  • 录用日期:2026-09-29
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