Calreticulin as a potential diagnostic biomarker for lung cancer
Calreticulin as a potential diagnostic biomarker for lung cancer
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钙网蛋白作为肺癌的潜在诊断生物标志物。
DOI：
10.1007/s00262-011-1146-8
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发表时间：
2012-06-01
影响因子：
5.8
通讯作者：
Jin, Boquan
中科院分区：
文献类型：
--
作者：
Liu, Rongrong;Gong, Jiuyu;Jin, Boquan
钙网蛋白（CRT）是一种内质网腔钙结合伴侣蛋白。用重组片段（rCRT/39-272）免疫小鼠，获得6株单克隆抗体（mAb）。基于这些单克隆抗体，微板荧光酶免疫分析（CLEIA）系统的测量检测限为0.09 ng/ml的开发。应用CLEIA系统检测58例肺癌患者血清中可溶性CRT（sCRT）含量，发现其显著高于40例健康人（仅9例可检出，P < 0.0001）。其中小细胞肺癌血清sCRT低于腺癌（P = 0.0085），均低于鳞癌（P = 0.013，P = 0.0012）。化疗后患者血清sCRT水平明显高于未化疗患者（P = 0.042）。免疫组化进一步研究显示，CRT在肺癌细胞的胞浆和胞膜上也有高表达，而在正常肺细胞中有微量的CRT表达。相应地，肺癌细胞膜上CRT的表达水平与肿瘤病理分级相关。本研究表明，肺癌患者血清中sCRT浓度高于健康人血清，肺癌细胞膜上CRT表达水平与肿瘤病理分型和分级有关。这些结果表明CRT可作为肺癌预测和诊断的生物标志物。
Calreticulin (CRT) is an endoplasmic reticulum luminal Ca2+-binding chaperone protein. By immunizing mice with recombinant fragment (rCRT/39-272), six clones of monoclonal antibodies (mAbs) were generated and characterized. Based on these mAbs, a microplate chemiluminescent enzyme immunoassay (CLEIA) system with a measured limit of detection of 0.09 ng/ml was developed. Using this CLEIA system, it was found that soluble CRT (sCRT) level in serum samples from 58 lung cancer patients was significantly higher than that from 40 healthy individuals (only 9 were detectable, P < 0.0001). Among them, serum sCRT in the small cell lung cancer was lower than that in adenocarcinoma (P = 0.0085), while both were lower than that in the squamous cell carcinoma (P = 0.013, P = 0.0012, respectively). Moreover, it was found that sCRT in sera from the patients after chemotherapy was higher than that from the patients without chemotherapy (P = 0.042). Further study by immunohistochemistry showed that CRT was also highly expressed in the cytoplasm and on the membrane of the lung cancer cells, while there was a trace amount of CRT expression in normal lung cells. Correspondingly, the expression level of CRT on lung cancer cell membrane was associated with the tumor pathological grade. This study demonstrates that sCRT concentration in sera of lung cancer patients is higher than that in sera of healthy individuals, and CRT expression level on lung cancer cell membrane is associated with tumor pathological classification and grade. These findings suggest that CRT may be used as a biomarker in lung cancer prediction and diagnosis.