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血清狐猴酪氨酸激酶-3:一种用于筛查原发性非小细胞肺癌和预测癌症进展的新型生物标志物。

Serum lemur tyrosine kinase-3: a novel biomarker for screening primary non-small cell lung cancer and predicting cancer progression.

作者信息

Zhang Kexin, Chen Lujun, Deng Haifeng, Zou Yongyi, Liu Juan, Shi Hongbing, Xu Bin, Lu Mingyang, Li Chong, Jiang Jingting, Wang Zhigang

机构信息

Department of Respiratory, Third Affiliated Hospital of Soochow University Changzhou 213003, China.

Department of Tumor Biological Treatment, Third Affiliated Hospital of Soochow University Changzhou 213003, China.

出版信息

Int J Clin Exp Pathol. 2015 Jan 1;8(1):629-35. eCollection 2015.

Abstract

PURPOSE

We aimed to determine the expression level of serum soluble lemur tyrosine kinase-3 (sLMTK3) in human non-small cell lung cancer (NSCLC), and to examine whether the s sLMTK3 level could be used as a biomarker to screen primary NSCLC and to predict lung cancer progression.

METHODS

Serum levels of sLMTK3 in 67 patients with primary NSCLC, 28 patients with lung benign lesion, and 53 healthy volunteers were measured by sandwich ELISA. LMTK3 protein expression in NSCLC tissues and normal lung tissues was also detected by using immunohistochemical staining. Receiver operating characteristic (ROC) curve was selected to evaluate the sensitivity and the specificity of serum sLMTK3 level.

RESULTS

The mean concentration of sLMTK3 in NSCLC group was significantly higher than in the lung benign lesion group (P < 0.001) and the healthy control group (P < 0.001). Higher sLMTK3 level was correlated with age (P = 0.013), tumor-node-metastasis (TNM) stage (P < 0.001), and lymph node metastasis (P < 0.001) of NSCLC. In contrast to the normal lung tissues, increased LMTK3 expression was found in the NSCLC tissues, and was mainly located on the cytoplasm and the nuclei of cancer cells. For separating NSCLC from control group, the corresponding areas under the ROC curve (AUC) were 0.947 for sLMTK3 and 0.804 for CEA. With cutoffs of 10.05 ng/ml for sLMTK3 and 5.0 ng/ml for CEA respectively, the sensitivity and the specificity of sLMTK3 and CEA were, 80.60% and 97.53%, 35.82% and 96.30%, respectively, indicating better diagnostic value of sLMTK3.

CONCLUSIONS

The sLMTK3 level was significantly increased in human NSCLC, and could be used as a potential and valuable biomarker for screening primary NSCLC and for predicting the progression of patients with this malignancy.

摘要

目的

我们旨在确定血清可溶性狐猴酪氨酸激酶-3(sLMTK3)在人类非小细胞肺癌(NSCLC)中的表达水平,并研究sLMTK3水平是否可作为筛查原发性NSCLC及预测肺癌进展的生物标志物。

方法

采用夹心ELISA法检测67例原发性NSCLC患者、28例肺部良性病变患者及53名健康志愿者血清中sLMTK3水平,并采用免疫组化染色检测NSCLC组织和正常肺组织中LMTK3蛋白表达。采用受试者工作特征(ROC)曲线评估血清sLMTK3水平的敏感性和特异性。

结果

NSCLC组sLMTK3的平均浓度显著高于肺部良性病变组(P<0.001)和健康对照组(P<0.001)。较高的sLMTK3水平与NSCLC患者的年龄(P=0.013)、肿瘤-淋巴结-转移(TNM)分期(P<0.001)及淋巴结转移(P<0.001)相关。与正常肺组织相比,NSCLC组织中LMTK3表达增加,主要位于癌细胞的细胞质和细胞核。对于区分NSCLC与对照组,sLMTK3的ROC曲线下相应面积(AUC)为0.947,癌胚抗原(CEA)为0.804。sLMTK3和CEA的截断值分别为10.05 ng/ml和5.0 ng/ml时,sLMTK3和CEA的敏感性和特异性分别为80.60%和97.53%、35.82%和96.30%,表明sLMTK3具有更好的诊断价值。

结论

人类NSCLC中sLMTK3水平显著升高,可作为筛查原发性NSCLC及预测该恶性肿瘤患者病情进展的潜在有价值生物标志物。

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