非小细胞肺癌PD-L1蛋白表达与18F-FDG PET/CT代谢指标的关系研究

Relationship between PD-L1 protein expression and 18F-FDG PET/CT metabolic markers in non-small cell lung cancer

  • 摘要:
    目的 探讨非小细胞肺癌(NSCLC)组织中程序性死亡配体1(PD-L1)蛋白表达与18F-氟脱氧葡萄糖(FDG) PET/CT代谢指标之间的关系,为NSCLC的免疫治疗提供PET/CT代谢层面的理论依据。
    方法 回顾性收集并分析2020年1月至2021年7月于青岛大学第三临床医学院(青岛市市立医院)行18F-FDG PET/CT检查并被组织病理学检查(穿刺活体检查或手术)结果证实的55例NSCLC患者的临床资料,其中男性34例、女性21例,年龄(66.5±9.3)岁。 18F-FDG PET/CT检查于治疗前进行,采用PET体积计算机辅助判读图像处理系统对肺癌原发病灶行代谢指标的测定,包括最大标准化摄取值(SUVmax)、病灶糖酵解总量(TLG)和肿瘤代谢体积(MTV)。以PD-L1蛋白表达阳性的肿瘤细胞比例分数(TPS)=1%为临界值,将患者分为PD-L1蛋白表达阳性组(TPS≥1%)和阴性组(TPS<1%);以PD-L1蛋白表达阳性的TPS=50%为临界值,将阳性组患者分为PD-L1蛋白高表达组(TPS≥50%)和低表达组(1%≤TPS<50%)。符合正态分布的计量资料的组间比较采用两独立样本t检验;计数资料的组间比较采用卡方检验;对病灶SUVmax与PD-L1蛋白表达情况的关系行Pearson相关分析;对病灶TLG和MTV与PD-L1蛋白表达情况的关系行Spearman秩相关分析。勾画受试者工作特征(ROC)曲线,以SUVmax的最佳临界值将入组患者分为高SUVmax组与低SUVmax组,观察2组的PD-L1蛋白表达情况。
    结果 NSCLC病灶SUVmax与PD-L1蛋白表达阳性的TPS呈正相关(r=0.604,P<0.001);而MTV和TLG与TPS均无相关性(r=0.083、0.102,均P>0.05)。55例患者中,PD-L1蛋白表达阳性组34例、阴性组21例,阳性组SUVmax高于阴性组(12.58±6.35 对 5.60±4.83,t=2.576,P<0.05)。ROC曲线结果显示,以SUVmax=5.15为最佳临界值,高SUVmax组36例、低SUVmax组19例,2组PD-L1蛋白表达阳性率分别为80.56%(29/36)和28.16%(5/19),PD-L1蛋白表达阳性的TPS分别为12.50%±3.21%和1.28%±0.46%,高SUVmax组患者PD-L1蛋白表达阳性率及TPS均更高,且差异均有统计学意义(χ2=15.500,t=2.671,均P<0.05)。
    结论 NSCLC患者18F-FDG PET/CT中SUVmax与PD-L1蛋白表达阳性的TPS呈正相关,可为NSCLC的免疫治疗提供依据。

     

    Abstract:
    Objective To investigate the relationship between programmed death-ligand 1 (PD-L1) protein expression in non-small cell lung cancer (NSCLC) tissues and 18F-fluorodeoxyglucose (FDG) PET/CT metabolic markers and to provide theoretical basis for NSCLC immunotherapy on PET/CT metabolic level.
    Methods The clinical data of 55 patients with NSCLC who underwent 18F-FDG PET/CT from January 2020 to July 2021 in Third Clinical Medical College of Qingdao University (Qingdao Municipal Hospital) and confirmed by histopathological examination (biopsy or surgery) were retrospectively collected and analyzed, including 34 males and 21 females, aged (66.5±9.3) years. 18F-FDG PET/CT examination was performed before treatment. The metabolic parameters of primary lung cancer lesions were measured using the PET volume computed assisted reading (VCAR) image processing system, including maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and metabolic tumor volume (MTV). Taking the tumor proportion score (TPS) of tumor cells with a positive PD-L1 protein expression=1% as the threshold, patients were divided into positive PD-L1 protein expression group (TPS≥1%) and negative group (TPS<1%). With the threshold of TPS=50% for PD-L1 protein expression, patients in the positive group were divided into high PD-L1 protein expression group (TPS≥50%) and low expression group (1%≤TPS<50%). Two independent sample t-test was performed for the intergroup comparison of measurement data in accordance with normal distribution. Chi-square test was conducted for the intergroup comparison of counting data. Pearson correlation analysis was performed on the relationship between SUVmax and PD-L1 protein expression in lesions. Spearman rank correlation analysis was conducted on the relationship among TLG, MTV, and PD-L1 protein expression in lesions. The receiver operating characteristic (ROC) curve was drawn. Enrolled patients were divided into high and low SUVmax groups on the basis of the optimal critical value of SUVmax. PD-L1 protein expression was observed in both groups.
    Results A positive correlation was found between SUVmax and TPS of tumor cells with a positive PD-L1 protein expression in NSCLC lesions (r=0.604, P<0.001); no correlation was observed between MTV, TLG, and TPS (r=0.083, 0.102, both P>0.05). Among 55 patients, 34 were in the positive PD-L1 protein expression group and 21 in the negative group. The SUVmax in the positive group was higher than that in the negative group (12.58±6.35 vs. 5.60±4.83, t=2.576, P<0.05). The ROC curve results revealed that with SUVmax=5.15 as the optimal critical value, 36 cases were found in the high SUVmax group and 19 cases in the low SUVmax group. The positive expression rates of PD-L1 protein in the two groups were 80.56% (29/36) and 28.16% (5/19). The TPS of tumor cells with a positive PD-L1 protein expression were 12.50%±3.21% and 1.28%±0.46%, respectively. Patients in the high SUVmax group had a higher positive expression rates of PD-L1 protein and TPS, and the differences were statistically significant (χ2=15.500, t=2.671, both P<0.05).
    Conclusion A positive correlation is found between SUVmax in 18F-FDG PET/CT and TPS of tumor cells with a positive PD-L1 protein expression in patients with NSCLC, which can provide evidence for NSCLC immunotherapy.

     

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