P-糖蛋白/多药耐药基因1信使核糖核酸、多药耐药相关蛋白及肺耐药蛋白在非霍奇金淋巴瘤中的表达及意义

[Expression and significance of P-gp/mdr1 mRNA, MRP and LRP in non-Hodgkin's lymphoma].

作者信息

Li Le, Su Li-ping, Ma Li, Zhao Jin, Zhu Lei, Zhou Yong-an

机构信息

Department of Haematology, Shanxi Tumor Hospital, Taiyuan 030013, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2009 Mar;31(3):199-202.

PMID:19615260

Abstract

OBJECTIVE

To explore the expression and clinical significance of P-glycoprotein (P-gp)/mdr1mRNA, multidrug resistance-associated protein (MRP) and lung resistance protein (LRP) in newly diagnosed non-Hodgkin's lymphoma.

METHODS

mdr1 mRNA of in 41 patients with non-Hodgkin's lymphoma was assayed by semi-quantitative RT-PCR. The expressions of P-gp, MRP and LRP proteins in lymph node viable blasts were identified by flow cytometry. The results were compared with those obtained from control cases, and the correlation of the changes with clinical outcomes was analyzed.

RESULTS

(1) Among the 41 cases, the positive expression of P-gp protein was detected in 8 cases, MRP in 7 cases, LRP in 15 cases, and mdr 1 mRNA in 11 cases. (2) The P-gp and LRP levels in NHL were significantly higher than those in control group, but MRP wasn't. The P-gp over-expression was significantly associated with mdr1mRNA (r = 0.396, P = 0.01). No correlation was showed among the expressions of P-gp, MRP and LRP. (3) Patients with P-gp expression had a poorer outcome of chemotherapy than those with P-gp-negative (P = 0.005). P-gp expression was significantly associated with higher clinical stage (P = 0.046) and elevated serum lactate dehydrogenase level (P = 0.032), but not associated with malignant degree (P = 0.298). MRP had no impact on the outcome of chemotherapy (P = 0.212), and wasn't significantly associated with higher clinical stage (P = 0.369), elevated LDH (P = 0.762) and higher malignant degree (P = 0.451). Patients with LRP expression had a poorer outcome of chemotherapy than those LRP-negative (P = 0.012). LRP expression was significantly associated with higher clinical stage (P = 0.0019), elevated LDH (P = 0.02) and higher malignant degree (P = 0.01).

CONCLUSION

The data of this study indicate that P-gp and LRP expressions but not MRP expression are important in the mechanism of drug resistance associated with a poor clinical outcome in previously untreated NHL.

摘要

目的

探讨P-糖蛋白（P-gp）/mdr1mRNA、多药耐药相关蛋白（MRP）及肺耐药蛋白（LRP）在初诊非霍奇金淋巴瘤中的表达及临床意义。

方法

采用半定量逆转录聚合酶链反应（RT-PCR）检测41例非霍奇金淋巴瘤患者的mdr1mRNA。采用流式细胞术检测淋巴结活细胞中P-gp、MRP及LRP蛋白的表达。将结果与对照组进行比较，并分析其变化与临床结局的相关性。

结果

（1）41例患者中，P-gp蛋白阳性表达8例，MRP阳性表达7例，LRP阳性表达15例，mdr1mRNA阳性表达11例。（2）非霍奇金淋巴瘤患者的P-gp和LRP水平显著高于对照组，但MRP水平无差异。P-gp过表达与mdr1mRNA显著相关（r = 0.396，P = 0.01）。P-gp、MRP和LRP的表达之间无相关性。（3）P-gp表达阳性的患者化疗效果较P-gp阴性患者差（P = 0.005）。P-gp表达与较高的临床分期（P = 0.046）和血清乳酸脱氢酶水平升高（P = 0.032）显著相关，但与恶性程度无关（P = 0.298）。MRP对化疗效果无影响（P = 0.212），与较高的临床分期（P = 0.369）、乳酸脱氢酶升高（P = 0.762）和较高的恶性程度（P = 0.451）无显著相关性。LRP表达阳性的患者化疗效果较LRP阴性患者差（P = 0.012）。LRP表达与较高的临床分期（P = 0.0019）、乳酸脱氢酶升高（P = 0.02）和较高的恶性程度（P = 0.01）显著相关。