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

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.

Keywords: Lemur tyrosine kinase-3; estrogen receptor; non-small cell lung cancer; tumor biomarker.

Figure 1

Serum sLMTK3 levels in patients with NSCLC, lung benign lesion and healthy controls. Significantly elevated sLMTK3 levels were found in NSCLC patients compared with that in patients with lung benign lesion or healthy controls (P < 0.001).

Figure 2

Immunohistochemical analysis of LMTK3 expression in lung cancer and normal lung tissues. A, B. LMTK3 protein was strongly expressed in the cytoplasm and in the nucleus of the lung squamous cell carcinoma as well as the lung adenocarcinoma, respectively; C. LMTK3 protein was weakly expressed in the cytoplasm of normal lung tissues. (× 200 magnification, Scale bar, 100 μm, Lecia DM 2500).

Figure 3

ROC curve analysis of sLMTK3 and CEA as serum markers to separate NSCLC patients from control group.