PLA2G16 Expression in Human Osteosarcoma Is Associated with Pulmonary Metastasis and Poor Prognosis

PLoS One. 2015 May 18;10(5):e0127236. doi: 10.1371/journal.pone.0127236. eCollection 2015.

Abstract

Background: Osteosarcoma is the most frequent type of malignant bone tumor in children and adolescents and is associated with a high propensity for lung metastasis. Recent experiments have indicated that PLA2G16 contributes to osteosarcoma progression and metastasis in both mouse and human osteosarcoma cell lines. The aim of this study was to compare the expression of PLA2G16 in non-metastatic and metastatic osteosarcomas to determine whether PLA2G16 expression can serve as a biomarker of osteosarcoma prognosis and metastasis.

Methods: Quantitative real-time PCR was used to examine PLA2G16 mRNA in primary osteosarcoma patients (18 patients without metastases and 17 patients with metastases), and immunohistochemistry (IHC) staining of PLA2G16 was performed on tissue microarrays from 119 osteosarcoma patients. Tumor metastatic behavior and survival of the patients were followed up for a minimum of 36 months and a maximum of 171 months. The prognostic value of PLA2G16 expression was evaluated by the Kaplan-Meier method and a log-rank test. Multivariate Cox regression analysis was used to identify significant independent prognostic factors.

Results: Osteosarcoma patients with metastasis showed a higher expression of PLA2G16 at both the mRNA and protein levels (both at P values< 0.05) than did patients without metastasis. Osteosarcoma patients with positive IHC staining of PLA2G16 expression at primary sites had shorter overall survival and metastasis-free survival (both at P values <0.02). Moreover, multivariate Cox analysis identified PLA2G16 expression as an independent prognostic factor to predict poor overall survival and metastasis-free survival (both P values < 0.03).

Conclusions: This study indicated that PLA2G16 expression is a significant prognostic factor in primary osteosarcoma patients for predicting the development of metastases and poor survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Male
  • Neoplasm Metastasis
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • Phospholipases A2, Calcium-Independent / genetics*
  • Phospholipases A2, Calcium-Independent / metabolism*
  • Prognosis
  • Survival Analysis
  • Tissue Array Analysis
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Tumor Suppressor Proteins
  • PLAAT3 protein, human
  • Phospholipases A2, Calcium-Independent

Grants and funding

This work was supported by the Program for National Clinical Research Center of Cancer. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.