Macrophage migration inhibitory factor and stearoyl-CoA desaturase 1: potential prognostic markers for soft tissue sarcomas based on bioinformatics analyses

PLoS One. 2013 Oct 22;8(10):e78250. doi: 10.1371/journal.pone.0078250. eCollection 2013.

Abstract

The diagnosis and treatment of soft tissue sarcomas (STSs) has been particularly difficult, because STSs are a group of highly heterogeneous tumors in terms of histopathology, histological grade, and primary site. Recent advances in genome technologies have provided an excellent opportunity to determine the complete biological characteristics of neoplastic tissues, resulting in improved diagnosis, treatment selection, and investigation of therapeutic targets. We had previously developed a novel bioinformatics method for marker gene selection and applied this method to gene expression data from STS patients. This previous analysis revealed that the extracted gene combination of macrophage migration inhibitory factor (MIF) and stearoyl-CoA desaturase 1 (SCD1) is an effective diagnostic marker to discriminate between subtypes of STSs with highly different outcomes. In the present study, we hypothesize that the combination of MIF and SCD1 is also a prognostic marker for the overall outcome of STSs. To prove this hypothesis, we first analyzed microarray data from 88 STS patients and their outcomes. Our results show that the survival rates for MIF- and SCD1-positive groups were lower than those for negative groups, and the p values of the log-rank test are 0.0146 and 0.00606, respectively. In addition, survival rates are more significantly different (p = 0.000116) between groups that are double-positive and double-negative for MIF and SCD1. Furthermore, in vitro cell growth inhibition experiments by MIF and SCD1 inhibitors support the hypothesis. These results suggest that the gene set is useful as a prognostic marker associated with tumor progression.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / biosynthesis*
  • Computational Biology*
  • Disease-Free Survival
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intramolecular Oxidoreductases / biosynthesis*
  • Macrophage Migration-Inhibitory Factors / biosynthesis*
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Oligonucleotide Array Sequence Analysis
  • Sarcoma* / metabolism
  • Sarcoma* / mortality
  • Soft Tissue Neoplasms* / metabolism
  • Soft Tissue Neoplasms* / mortality
  • Stearoyl-CoA Desaturase / biosynthesis*
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Macrophage Migration-Inhibitory Factors
  • Neoplasm Proteins
  • SCD1 protein, human
  • Stearoyl-CoA Desaturase
  • Intramolecular Oxidoreductases
  • MIF protein, human

Grant support

This work was supported by the Ministry of Education, Culture and Sports, Science and Technology of Japan [Grants-in-Aid for Scientific Research to Young Scientists (B) (No. 21710211 and 24710222 to HT) and by Futaba Electronics Memorial Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.