Tuberc Respir Dis.  2013 Sep;75(3):104-110.

Plasma Osteopontin Is a Useful Diagnostic Biomarker for Advanced Non-Small Cell Lung Cancer

Affiliations
  • 1Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea. pulmo2@kangwon.ac.kr
  • 2Department of Otolaryngology, Kangwon National University School of Medicine, Chuncheon, Korea.
  • 3The Research Department, Kangwon Regional Cancer Center, Kangwon National University Hospital, Chuncheon, Korea.
  • 4The Clinical Research Institute of Kangwon National University Hospital, Chuncheon, Korea.

Abstract

BACKGROUND
Osteopontin (OPN) and carbonic anhydrase IX (CAIX), which are expressed on the surface of tumor cells, are associated with hypoxia during tumor development and progression. However, the roles of these proteins in the plasma of patients with non-small cell lung cancer (NSCLC) are poorly understood. Herein, we hypothesized that plasma OPN and CAIX levels could be used as diagnostic and prognostic tumor markers in patients with NSCLC.
METHODS
Fifty-three patients with NSCLC and 50 healthy control subjects were enrolled. We selected controls without malignancy and matched them with NSCLC patient cases according to age and gender. Blood samples were collected at the time of diagnosis; the plasma levels of OPN and CAIX were measured by enzyme-linked immunosorbent assays.
RESULTS
The plasma levels of OPN in the patients with NSCLC were significantly elevated as compared to those in the controls (p=0.016). However, there was no difference in the plasma level of CAIX between the NSCLC patients and controls. NSCLC patients with a distant metastasis had a remarkable increase in plasma OPN compared with patients without metastasis (p=0.026), but no such correlation was found for CAIX. There was no difference in overall survival rates according to the plasma level of OPN between the two groups (by Kaplan-Meier survival analysis).
CONCLUSION
Plasma OPN levels were elevated in patients with NSCLC as compared with the controls, with greater elevation of OPN levels in the advanced stages of disease. Therefore, plasma OPN may have utility as a diagnostic, but not prognostic, biomarker of advanced NSCLC.

Keyword

Osteopontin; CA9 Protein, Human; Lung Neoplasms

MeSH Terms

Anoxia
Antigens, Neoplasm
Carbonic Anhydrases
Carcinoma, Non-Small-Cell Lung
Humans
Lung Neoplasms
Neoplasm Metastasis
Osteopontin
Plasma
Proteins
Survival Rate
Biomarkers, Tumor
Antigens, Neoplasm
Carbonic Anhydrases
Osteopontin
Proteins

Figure

  • Figure 1 Box plots depicting plasma levels of osteopontin (OPN) according to distant metastasis. The box plots indicate the levels of OPN in individual plasma samples. The box is bound above and below by the 75th and 25th percentiles, respectively. The horizontal line within the box indicates the median plasma OPN level. The upper and lower horizontal bars indicate the maximal and minimal levels, respectively. The circles show outliers. The plasma levels of OPN were elevated in patients with distant metastasis. *p<0.05 by the Mann-Whitney U test. NS: not significant.

  • Figure 2 Receiver operating characteristic curve analysis of the plasma osteopontin levels in the non-small cell lung cancer patients and controls.

  • Figure 3 Kaplan-Meier survival curves according to plasma osteopontin (OPN) levels in patients with non-small cell lung cancer (NSCLC). Overall survival curves of patients with plasma OPN levels higher or lower than the median plasma OPN level (93.07 ng/mL). The solid line indicates the cumulative survival of patients with higher OPN levels, and the dashed line indicates the cumulative survival of patients with lower OPN levels. N: number of patients.


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