[肺癌中与多药耐药及化疗耐药相关的蛋白质表达]

[Expression of proteins associated with multidrug resistance and resistance to chemotherapy in lung cancer].

作者信息

Paredes Lario Alfredo, Blanco García Carlos, Echenique Elizondo Miguel, Lobo Carmen

机构信息

Servicio de Oncología, Hospital Donostia, San Sebastián, Guipúzcoa, España.

出版信息

Arch Bronconeumol. 2007 Sep;43(9):479-84.

PMID:17919413

Abstract

OBJECTIVE

Membrane transporters are proteins that play a crucial role in resistance to chemotherapy. The aim of this study was to assess the influence of membrane transporter protein expression on chemotherapeutic response.

MATERIAL AND METHODS

One hundred and forty seven samples of tumor tissue were collected from 143 patients; 35 samples were obtained by bronchoscopy and 112 were surgical specimens. A total of 101 samples from 99 patients were adequate for study. Cryopreserved samples were subjected to immunohistochemical analysis to detect 3 proteins associated with multidrug resistance: P-glycoprotein (Pgp), multidrug-resistance-associated protein 1 (MRP1), and lung resistance protein (LRP).

RESULTS

In 16 cases none of the proteins were expressed. A single protein was expressed in 32 (3 Pgp, 11 MRP1, and 18 LRP); 2 in 34 cases (24 Pgp and LRP; 5 MRP1 and Pgp; 5 MRP1 and LRP); and all 3 in 17 cases. No significant relationship was found between age and the expression of Pgp (P=.74), MRP1 (P=.95), or LRP (P=.26). Nor were there significant differences in number (P=.72) or type of coexpressed proteins (P=.39) by sex, by tumor stage (number, P=.55; type, P=.21), or by tumor grade (number, P=.59; type, P=.51). There was a highly significant trend toward coexpression of Pgp and LRP (P< .01) but not of Pgp and MRP1 (P=.18) or MRP1 and LRP (P=.26). MRP1 was expressed less often in adenocarcinoma. LRP was expressed less often in squamous cell carcinoma than in adenocarcinoma and undifferentiated large cell carcinoma. Coexpression of Pgp, MRP1, and LRP was observed most often in squamous cell carcinoma.

CONCLUSIONS

Proteins associated with multidrug resistance are commonly expressed in lung cancer. Of the 3 proteins studied, LRP was the one most often found. Coexpression of more than 1 of the proteins was found in a considerable percentage of patients. Pgp was mainly found to be coexpressed with LRP. Pgp expression and the number of coexpressed proteins seemed to have a negative impact on response to chemotherapy.

摘要

目的

膜转运蛋白是在化疗耐药中起关键作用的蛋白质。本研究旨在评估膜转运蛋白表达对化疗反应的影响。

材料与方法

从143例患者中收集了147份肿瘤组织样本；35份样本通过支气管镜检查获得，112份为手术标本。来自99例患者的总共101份样本适合进行研究。对冷冻保存的样本进行免疫组织化学分析，以检测与多药耐药相关的3种蛋白质：P-糖蛋白（Pgp）、多药耐药相关蛋白1（MRP1）和肺耐药蛋白（LRP）。

结果

16例中无蛋白质表达。32例（3例Pgp、11例MRP1和18例LRP）表达单一蛋白质；34例表达2种蛋白质（24例Pgp和LRP；5例MRP1和Pgp；5例MRP1和LRP）；17例表达所有3种蛋白质。未发现年龄与Pgp（P = 0.74）、MRP1（P = 0.95）或LRP（P = 0.26）表达之间存在显著关系。按性别、肿瘤分期（数量，P = 0.55；类型，P = 0.21）或肿瘤分级（数量，P = 0.59；类型，P = 0.51）划分，共表达蛋白质的数量（P = 0.72）或类型（P = 0.39）也无显著差异。Pgp和LRP共表达有高度显著趋势（P < 0.01），但Pgp和MRP1（P = 0.18）或MRP1和LRP（P = 0.26）无此趋势。MRP1在腺癌中表达较少。LRP在鳞状细胞癌中的表达频率低于腺癌和未分化大细胞癌。Pgp、MRP1和LRP的共表达在鳞状细胞癌中最常见。