Yang Kun, Xu Jing, Liu Qinghang, Li Jing, Xi Yanfeng
Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi Province, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
Pathol Res Pract. 2019 Feb;215(2):265-271. doi: 10.1016/j.prp.2018.10.021. Epub 2018 Nov 2.
Although dose intensification strategies achieve a favorable prognosis for pediatric patients of T-lmphoblastic lymphoma/leukemia (T-LBL/ALL), numerous side effects have been followed. Molecular targeted therapies will be needed to optimize the current treatment strategy for T-LBL/ALL. The aim of this study was to analyse expression and significance of CD47, PD1 and PDL1 in. T-LBL/ALL. We performed immunohistochemistry staining and real time fluorescence quantitative PCR (qRT-PCR) on FFPE tissues. Immunohistochemistry results showed that the high expression rate of CD47 protein was 46.4% (26/56) and the positive expression rate of PDL1 protein was 37.5% (21/56). PD1 expression was observed in tumor infiltrating lymphocytes in approximately 20% of T-LBL/ALL patients, but not expressed on tumor cells of T-LBL/ALL. And the results of qRT-PCR showed that the relative expression levels of CD47, PDL1 and PD1 mRNA in 56 cases of T LBL/ALL were significantly higher than those in control group (6.915 vs 4.050, 12.255 vs 2.575, 37.990 vs 3.615), and the differences were all statistically significant (p all <0.05). Univariate analysis showed that age, CD47 protein, CD47 mRNA,PDL1 protein and PDL1 mRNA expression were closely correlated with prognosis (P all <0.05). We found that the overall one-year survival rates of patients with a high expression (≥M) of CD47 and PDL1 mRNA were higher than in patients with low expression (<M). However, the overall one-year survival rate of patients with a high expression (≥M) of CD47 and PDL1 protein were lower than in patients with low expression (<M). And patients with ≤25 years old had a worse prognosis than with >25 years old. Multivariate Cox regression analysis showed that the high expression of CD47 and PDL1 protein were independent prognostic factors (both p < 0.05). In a word, PD1/PDL1 and CD47 may be involved in the disease progression and prognosis of T-LBL/ALL, and detection and targeting of CD47 and PD1/PDL1 may provide a rational basis to for treatment of T-LBL/ALL.
尽管剂量强化策略能使T淋巴细胞母细胞淋巴瘤/白血病（T-LBL/ALL）患儿获得较好的预后，但也随之出现了许多副作用。因此，需要分子靶向治疗来优化目前T-LBL/ALL的治疗策略。本研究旨在分析CD47、PD1和PDL1在T-LBL/ALL中的表达及意义。我们对福尔马林固定石蜡包埋（FFPE）组织进行了免疫组织化学染色和实时荧光定量PCR（qRT-PCR）。免疫组织化学结果显示，CD47蛋白高表达率为46.4%（26/56），PDL1蛋白阳性表达率为37.5%（21/56）。在约20%的T-LBL/ALL患者的肿瘤浸润淋巴细胞中观察到PD1表达，但在T-LBL/ALL的肿瘤细胞上未表达。qRT-PCR结果显示，56例T-LBL/ALL患者中CD47、PDL1和PD1 mRNA的相对表达水平均显著高于对照组（分别为6.915 vs 4.050、12.255 vs 2.575、37.990 vs 3.615），差异均有统计学意义（P均<0.05）。单因素分析显示，年龄、CD47蛋白、CD47 mRNA、PDL1蛋白和PDL1 mRNA表达与预后密切相关（P均<0.05）。我们发现，CD47和PDL1 mRNA高表达（≥M）患者的总体一年生存率高于低表达（<M）患者。然而，CD47和PDL1蛋白高表达（≥M）患者的总体一年生存率低于低表达（<M）患者。并且年龄≤25岁的患者预后比>25岁的患者差。多因素Cox回归分析显示，CD47和PDL1蛋白高表达是独立的预后因素（均P<0.05）。总之，PD1/PDL1和CD47可能参与T-LBL/ALL的疾病进展和预后，检测并靶向CD47和PD1/PDL1可能为T-LBL/ALL的治疗提供合理依据。
