CXCL12/CXCR4与T淋巴母细胞淋巴瘤/白血病预后的相关性  

Significance of CXCL12/CXCR4 expression in T-iymphoblastic lymphoma/leukemia

作　　者：于转转 郗彦凤[2] 李静[1] 白文启[2] 高宁[2] 步鹏[2] Yu Zhuanzhuan Xi Yanfeng Li Jing Bai Wenqi Gao Ning Bu Peng(Shanxi Medical University, Taiyuan 030013, China)

机构地区：[1]山西医科大学基础医学院病理教研室,太原030013 [2]山西省肿瘤医院病理科

出　　处：《中华病理学杂志》2016年第12期838-843,共6页Chinese Journal of Pathology

基　　金：山西省自然科学基金（201601D011129,2011011038-1）

摘　　要：目的探讨CXCL12/CXCR4与T淋巴母细胞淋巴瘤/白血病（T－LBL/ALL）预后的相关性。方法选取72例T－LBL/ALL及30例淋巴结反应性增生（LH）患者标本作为对照，进行CXCL12、CXCR4和Ki－67等免疫组织化学（IHC）检测，并采用real－time RT－PCR法测量CXCL12和CXCR4 mRNA表达量。结果（1）IHC结果：T－LBL/ALL中CXCL12和CXCR4表达阳性率分别为84.7%（61/72）和91.6%（66/72），与LH组相比，差异无统计学意义。Ki－67〈80%和≥80%分别为34.7%（25/72）和65.3%（47/72）。（2）real－time RT－PCR结果：T－LBL/ALL中CXCL12和CXCR4的mRNA相对表达量分别是LH组的62.4%和71.5%，差异有统计学意义（P〈0.05）。（3）单因素分析结果：在T－LBL/ALL中，CXCL12 mRNA表达量与Ann Arbor分期、卡氏评分呈正相关（P〈0.05）。CXCL12蛋白与脾肿大呈正相关（P〈0.05）。CXCR4 mRNA表达量与国际预后指数评分、临床症状、纵隔增宽、骨髓侵犯呈正相关（P〈0.05）。CXCR4蛋白与纵隔增宽呈正相关（P〈0.05）。CXCL12 mRNA表达量与CXCL12蛋白、CXCR4蛋白表达呈正相关（P〈0.05）。（4）多因素COX回归分析结果：CXCR4蛋白高表达、肝脾肿大和骨髓累犯均为影响T－LBL/ALL预后的危险因素。结论CXCL12/CXCR4表达与T－LBL/ALL的进展、纵隔增宽、骨髓侵犯和预后差等有关，提示趋化轴CXCL12/CXCR4在T－LBL/ALL的发生发展中起着必不可少的作用。然而，CXCL12和CXCR4的蛋白表达并不能完全由mRNA转录水平来反映，可能存在其他分子参与CXCL12/CXCR4的表达和调控。随着CXCR4拮抗剂进入临床试验，CXCL12/CXCR4可能成为改善T－LBL/ALL患者预后的治疗靶点。Objective To investigate the significance of CXCL12/CXCR4 expression in T lymphoblastic lymphoma/leukemia （T-LBL/ALL） and its prognostic significance. Methods Using immunohistochemical EnVision method, CXCL12, CXCR4 and Ki-67 expression were evaluated in 72 cases of T-LBL/ALL and 30 selected cases of lymph node reactive hyperplasia （ LH ） as control. In addition, CXCL12 and CXCR4 mRNA expression levels were examined by real-time reverse transcription polymerase chain reaction （real-time RT-PCR） method. Results Immunohistochemical results showed that the expression rates of CXCL12 and CXCR4 in T-LBL/ALL were 84. 7% （61/72） and 91.6% （66/72）, respectively, and these were not different from the expression in the LH control group. The expression indexes of Ki-67 〈 80% and ≥80% were 25 cases （34. 7% ,25/72） and 47 cases （65.3% ,47/72）, respectively. Real-time quantitative PCR demonstrated that CXCL12 and CXCR4 mRNA expression in T-LBL/ALL was 62. 4% and 71.5%, respectively, and was statistically different （P 〈 0. 05 ） from that of the control group. Single factor analysis found that CXCL12 mRNA expression in T-LBL/ALL was positively correlated with Ann Arbor staging and KPS score （ P 〈 0. 05 ） ; CXCL12 protein expression was positively correlated with splenomegaly （ P 〈 0. 05 ） ; CXCR4 mRNA expression was positively correlated with the IPI score, clinical symptoms, mediastinal widening and bone marrow involvement （ P 〈 0. 05 ） ; CXCR4 protein expression was positively correlated with mediastinal widening （P 〈 0.05 ） ; CXCL12 mRNA expression was positively correlated with CXCL12 protein and CXCR4 protein expression （ P 〈 0. 05 ）, but not the CXCR4 mRNA and protein levels. There was no correlation between CXCL12 and CXCR4 protein expression and CXCR4 mRNA expression. Multivariate COX regression analysis showed that high expression of CXCR4 protein, hepatosplenomegaly and bone marrow involvement were risk factors for T-LBIZALL outcome. Conclusions CXCL12

关 键 词：T淋巴母细胞淋巴瘤 国际预后指数 相关性 白血病 MRNA表达量 CXCL12 RT-PCR法 CXCR4 

分 类 号：R733[医药卫生—肿瘤]