Abstract
Midkine, a heparin-binding growth factor, has been identified as a promising cancer biomarker. In non-small cell lung cancer (NSCLC), the serum and urine midkine levels have not been intensively investigated. The aim of the present study was to investigate the diagnostic and prognostic potential of serum and urine midkine levels in patients with NSCLC. The serum midkine levels were measured in 153 patients with NSCLC, 23 patients with benign pulmonary disease and 95 healthy controls using ELISA. Urine midkine levels were examined in 20 controls and 45 patients with NSCLC. Midkine expression in tumor tissues from 72 patients with NSCLC who underwent definitive surgical resection without any pre-operative treatments was examined by immunohistochemistry. Serum levels were significantly higher in patients with NSCLC than in healthy controls (657.36±496.58 pg/ml vs. 194.49±122.57 pg/ml, P<0.001). As shown in the ROC curve analysis, the sensitivity and specificity of the cut-off serum midkine concentration of 400 pg/ml for predicting the presence of NSCLC were 71.2% and 88.1%, respectively. Positive correlations between the serum midkine levels and immunohistochemistry staining scores (r=0.315, P=0.007) and between the serum midkine levels and urine midkine levels (r=0.636, P<0.001) were observed using Spearman's bivariate correlations. The serum midkine concentration was identified as an independent prognostic factor by multivariate analysis, and its overexpression yielded a relative risk of death of 2.072 (0.01<P<0.05, 95%CI: 1.104-3.890). Thus, the serum and urine midkine levels may be useful, minimally invasive biomarkers for detecting and predicting the prognosis of NSCLC.
Highlights
Lung cancer is the leading type of cancer and cause of cancer mortality worldwide
The serum midkine levels in 153 patients with non-small cell lung cancer (NSCLC), 23 patients with benign pulmonary diseases and 95 healthy controls were analyzed using an ELISA to investigate the role of midkine as a tumor marker for NSCLC
The serum and urinary midkine concentrations were significantly elevated in patients with NSCLC compared with healthy normal samples and patients with non-malignant pulmonary diseases, consistent with a report on the use of midkine levels for determining the prognosis of patients with NSCLC by Yuan et al [15]
Summary
Lung cancer is the leading type of cancer and cause of cancer mortality worldwide. The incidence of non-small cell lung cancer (NSCLC), a major form of lung cancer, has increased in the past several decades [1]. Despite advancements in diagnosis and therapeutic strategies of lung cancer, only 15% survive more than 5 years in patients with NSCLC [2]. Concerns about the detection of early stage lung cancer have become an inevitable issue in decisions regarding treatment. Various cancers express significantly higher levels of the midkine protein in early stage tumor tissues than in adjacent normal tissues [5,6,7,8]. Because midkine is a secreted protein and enzyme immunoassays have been developed to detect this protein, an increase in the serum and urinary midkine levels has been reported in patients with various tumors [9, 10]. Serum and urinary midkine levels are potentially important tools for the surveillance and early diagnosis of malignancies
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