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

J Cancer Res Clin Oncol. 2013 Apr;139(4):543-9. doi: 10.1007/s00432-012-1359-z. Epub 2012 Dec 5.

Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: Measurement of cell-free MK mRNA levels in effusion supernatant yields a high diagnostic accuracy and a potential predictive value.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / metabolism
  • Cell Proliferation
  • Female
  • Humans
  • Male
  • Middle Aged
  • Midkine
  • Nerve Growth Factors / genetics*
  • Nerve Growth Factors / metabolism
  • Pleural Effusion, Malignant / diagnosis*
  • Pleural Effusion, Malignant / genetics
  • Pleural Effusion, Malignant / metabolism
  • Prognosis
  • Prospective Studies
  • RNA, Messenger / genetics
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Carcinoembryonic Antigen
  • MDK protein, human
  • Nerve Growth Factors
  • RNA, Messenger
  • Midkine