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

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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.

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Abbreviations

MK:

Midkine

CEA:

Carcinoembryonic antigen

LDH:

Lactate dehydrogenase

ADA:

Adenosine deaminase

AUC:

Area under the curve

ROC:

Receiver operating characteristic

CI:

Confidence interval

PPV:

Positive predictive value

NPV:

Negative predictive value

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81101552), the Natural Science Foundation of Jiangsu Province (BK2011571 and BK2012744), Specialized Research Fund for the Doctoral Program of Higher Education (20100091120002) and the Fund of the National Natural Science Foundation of China in Advance (1116021401).

Conflict of interest

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Immunology and Reproduction Biology Lab, Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China

    Mingming Lv, Ping Wang, Yueqiu Chen, Tingting Wang & Yayi Hou

  2. Central Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, Nanjing, 210093, China

    Yongbin Mou

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  1. Mingming Lv
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  2. Yongbin Mou
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  3. Ping Wang
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  4. Yueqiu Chen
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  5. Tingting Wang
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Correspondence to Tingting Wang or Yayi Hou.

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Lv, M., Mou, Y., Wang, P. et al. Diagnostic and predictive role of cell-free midkine in malignant pleural effusions. J Cancer Res Clin Oncol 139, 543–549 (2013). https://doi.org/10.1007/s00432-012-1359-z

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  • DOI: https://doi.org/10.1007/s00432-012-1359-z

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