血清CA125、CA19-9、CEA及外泌体PD-L1在晚期胃癌患者化疗疗效评估中的价值

Value of serum CA125, CA19-9, CEA, and exosomal PD-L1 in assessing chemotherapy efficacy in patients with advanced gastric cancer

摘要:

目的 探讨血清糖类抗原125（CA125）、糖类抗原19-9（CA19-9）、癌胚抗原（CEA）及外泌体程序性死亡配体1（PD-L1）在评估晚期胃癌患者化疗疗效中的应用价值。方法 本研究为回顾性研究，选取2019年2月—2020年2月于苏州市中西医结合医院确诊并接受化疗的52例晚期胃癌患者为观察组，根据化疗疗效分为敏感组（21例）与耐药组（31例）。收集两组晨间空腹外周静脉血，采用电化学发光免疫检测技术检测血清CA125、CA19-9、CEA水平，透射电镜观察外泌体形态，Western blotting检测外泌体标志物表达水平并对外泌体进行鉴定，用酶标仪检测外泌体PD-L1蛋白表达。结果 耐药组患者CA125、CEA和CA19-9水平均高于敏感组（P <0.05）。耐药组PD-L1蛋白相对表达量低于敏感组（P <0.05）。血清CA125水平（r_s =-0.697）、CEA水平（r_s =-0.829）、CA19-9水平（r_s =-0.850）与化疗疗效均呈负相关（P <0.05）；外泌体PD-L1蛋白相对表达量与化疗疗效呈正相关（r_s =0.721，P <0.05）。ROC曲线结果分析，血清CA125、CEA、CA19-9和外泌体PD-L1联合预测化疗疗效的敏感性为95.2%（95% CI：0.762，0.999），特异性为96.8%（95% CI：0.833，0.999），AUC为0.980（95% CI：0.945，1.000）。结论 血清CA125、CA19-9、CEA及外泌体PD-L1可作为评估晚期胃癌患者化疗疗效的有效生物标志物。

Abstract:

Objective To explore the value of serum carbohydrate antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), as well as exosomal PD-L1, in assessing the chemotherapy efficacy in patients with advanced gastric cancer.Methods This study retrospectively included 52 patients diagnosed with advanced gastric cancer and treated with chemotherapy from February 2019 to February 2020 at Suzhou Integrated Traditional Chinese and Western Medicine Hospital as the observation group. Based on the chemotherapy response, these patients were divided into a chemotherapy-sensitive group (21 patients) and a chemotherapy-resistant group (31 patients). Serum samples were collected from two groups of subjects using fasting peripheral venous blood obtained in the morning. Electrochemiluminescent immunoassay was employed to measure serum CA125, CA19-9 and CEA levels. Transmission electron microscopy was used to observe exosome morphology. Western blotting was used to assess the expression levels of exosome markers and to characterize the exosomes, while microplate assays measured the PD-L1 protein expression in the exosomes.Results Patients in the chemotherapy-resistant group had higher serum levels of CA125, CEA, and CA19-9 than those in the chemotherapy-sensitive group (P < 0.05). The relative expression of PD-L1 protein in exosomes was lower in the chemotherapy-resistant group compared with the chemotherapy-sensitive group (P < 0.05). Serum CA125 (r_s = -0.697), CEA (r_s = -0.829), and CA19-9 (r_s = -0.850) levels were negatively correlated with chemotherapy efficacy (P < 0.05), whereas the relative expression of exosomal PD-L1 protein was positively correlated with chemotherapy efficacy (r_s = 0.721, P < 0.05). Analysis of the ROC curves showed that the combined use of serum CA125, CEA, CA19-9, and exosomal PD-L1 to predict chemotherapy response yielded a sensitivity of 95.2% (95% CI: 0.762, 0.999), a specificity of 96.8% (95% CI: 0.833, 0.999), and an AUC of 0.980 (95% CI: 0.945, 1.000).Conclusion Serum CA125, CA19-9, CEA, and exosomal PD-L1 may serve as effective biomarkers for evaluating chemotherapy efficacy in patients with advanced gastric cancer.