Midkine mRNA level in peripheral blood mononuclear cells is a novel biomarker for primary non-small cell lung cancer: a prospective study

J Cancer Res Clin Oncol. 2013 Apr;139(4):557-62. doi: 10.1007/s00432-012-1357-1. Epub 2012 Dec 7.

Abstract

Background and objectives: Midkine (MK) mRNA was highly expressed in various human cancer tissues and cells. The present study aimed to investigate whether MK mRNA level in peripheral blood mononuclear cells (PBMC) could serve as a diagnostic biomarker for patients having primary non-small cell lung cancer (NSCLC).

Methods: MK mRNA level in PBMC from 87 patients with primary NSCLC, 35 patients with lung benign lesion (LEL), and 30 healthy volunteers was analyzed by real-time quantitative RT-PCR. The levels of serum carcinoembryonic antigen, carbohydrate antigen 125 (CA125), and neuron-specific enolase were detected by chemiluminescent microparticle enzyme immunoassay.

Results: PBMC MK mRNA level was significantly higher in patients with primary NSCLC than that in other groups (P < 0.001), while there was no significant difference between LEL patients and healthy volunteers (P > 0.05). Higher MK mRNA level was correlated with clinical stages (P = 0.026), differentiation (P = 0.025), and lymph node metastasis (P = 0.022) of NSCLC. Using a cutoff of 0.0063, the sensitivity and specificity of MK mRNA levels to differentiate between patients with NSCLC and patients with LEL were 57.47 and 93.33 %,and it were 56.32 and 93.33 % for patients with NSCLC and healthy volunteers, respectively. Furthermore, multivariate analysis indicated that PBMC MK mRNA level above the cutoff value presented a chance of 11-fold higher for NSCLC occurrence.

Conclusions: MK mRNA level in PBMC may be a potential non-invasive molecular marker for the diagnosis of primary NSCLC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / metabolism
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Case-Control Studies
  • Female
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lymphatic Metastasis
  • 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

Substances

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