Diagnostic and predictive role of cell-free midkine in malignant pleural effusions

The detection of circulating nucleic acids has long been explored for the diagnosis and prognosis of a variety of clinical conditions. The aim of this study was to detect the cell-free mRNA expression of midkine (MK) in patients with effusions and its potential diagnostic and predictive value. Effusions were collected prospectively from 168 patients. The cell-free RNA was extracted from effusions, and the mRNA expression of MK was detected using real-time PCR. The expression of carcinoembryonic antigen (CEA) and biochemical markers in effusions were also assayed. Primary cancer cells were isolated from the malignant effusions (n = 46). Compared with culture cell lines, the response of these cancer cells to chemotherapeutic agents was determined by CCK-8 assay. The expression of cell-free MK mRNA was significantly higher in the malignant group than in the benign group (0.13 vs 0.01, P < 0.001). The sensitivity and diagnostic accuracy of MK were 77.5 and 81.5 %, while a combination of CEA and MK reached 86.9 % sensitivity and 88.7 % accuracy. In addition, cell-free MK mRNA expression was significantly correlated with inhibitory rate of cisplatin (R = -0.72, P < 0.01). Measurement of cell-free MK mRNA levels in effusion supernatant yields a high diagnostic accuracy and a potential predictive value.