1 Department of Medical Oncology, Cancer Hospital of China Medical University , Liaoning Cancer Hospital & Institute, Shenyang, China .
2 Department of Medical Oncology, Key Laboratory of Liaoning Breast Cancer Research , Shenyang, China .
J Interferon Cytokine Res. 2018 May;38(5):213-220. doi: 10.1089/jir.2017.0146. Epub 2018 Apr 17.
Recombinant human thrombopoietin (rhTPO) is a key determinant of therapy for chemotherapy-induced thrombocytopenia (CIT) in patients with breast cancer. To assess the predictive value of preoperative inflammatory cells for response to rhTPO in breast cancer patients, a total of 198 female patients with breast cancer were enrolled between June 2011 and December 2016 in Liaoning Cancer Hospital. Peripheral blood samples before rhTPO therapy were obtained, the ratios of helper T cell (CD4), cytotoxic T cell (CD8), NK cell (CD16/CD56), and B cell (CD19) were analyzed, and CD4/CD8 ratios were calculated. The association between each marker and response to rhTPO was analyzed using the log-rank test. Of 198 patients, response was achieved in 151 (76.26%) patients. The predictive of CD4/CD8 ratio gave a sensitivity and specificity of 79% and 80% in the training cohort and a sensitivity and specificity of 73% and 87% in the test cohort, when the cutoff value was set to 1.56. Plasma levels of NK cell ratio and B cell ratio were similar in either responders or nonresponders for rhTPO. Plasma CD4/CD8 ratio was significantly lower in responders than in nonresponders for rhTPO (1.27 ± 0.49 vs. 2.24 ± 0.92, P < 0.05). Among 83 patients with grade 2 CIT, plasma CD4/CD8 ratio was lower significantly in rhTPO responders than in rhTPO nonresponders (1.19 ± 0.47 vs. 2.22 ± 1.11, P < 0.05) with 83% accuracy, but we observed little significant differences in patients with grade 3/4 CIT (1.32 ± 0.51 vs. 2.25 ± 0.77, P < 0.05) with 76% accuracy. Plasma CD4/CD8 ratio at baseline was significantly associated with response to rhTPO. We conclude that pretreatment CD4/CD8 ratio is a convenient, easily measured predictive indicator for patients with breast cancer receiving rhTPO, especially in patients with grade 2 CIT.
重组人血小板生成素（rhTPO）是乳腺癌患者化疗诱导血小板减少症（CIT）治疗的关键决定因素。为了评估术前炎症细胞对乳腺癌患者 rhTPO 反应的预测价值，2011 年 6 月至 2016 年 12 月共纳入辽宁省肿瘤医院 198 例女性乳腺癌患者。rhTPO 治疗前采集外周血样本，分析辅助 T 细胞（CD4）、细胞毒性 T 细胞（CD8）、自然杀伤细胞（CD16/CD56）和 B 细胞（CD19）的比例，并计算 CD4/CD8 比值。采用对数秩检验分析各标志物与 rhTPO 反应的关系。198 例患者中，151 例（76.26%）患者有反应。在训练队列中，CD4/CD8 比值的预测值在截值为 1.56 时的灵敏度和特异性分别为 79%和 80%，在测试队列中的灵敏度和特异性分别为 73%和 87%。rhTPO 反应者和无反应者的 NK 细胞比例和 B 细胞比例相似。rhTPO 反应者的血浆 CD4/CD8 比值明显低于无反应者（1.27±0.49 比 2.24±0.92，P<0.05）。在 83 例 2 级 CIT 患者中，rhTPO 反应者的血浆 CD4/CD8 比值明显低于 rhTPO 无反应者（1.19±0.47 比 2.22±1.11，P<0.05），准确率为 83%，但在 3/4 级 CIT 患者中观察到差异较小（1.32±0.51 比 2.25±0.77，P<0.05），准确率为 76%。基线时的血浆 CD4/CD8 比值与 rhTPO 反应显著相关。我们得出结论，预处理 CD4/CD8 比值是接受 rhTPO 治疗的乳腺癌患者的一种方便、易于测量的预测指标，特别是在 2 级 CIT 患者中。
