Alterations in gene expression of proprotein convertases in human lung cancer have a limited number of scenarios

PLoS One. 2013;8(2):e55752. doi: 10.1371/journal.pone.0055752. Epub 2013 Feb 7.

Abstract

Proprotein convertases (PCs) is a protein family which includes nine highly specific subtilisin-like serine endopeptidases in mammals. The system of PCs is involved in carcinogenesis and levels of PC mRNAs alter in cancer, which suggests expression status of PCs as a possible marker for cancer typing and prognosis. The goal of this work was to assess the information value of expression profiling of PC genes. Quantitative polymerase chain reaction was used for the first time to analyze mRNA levels of all PC genes as well as matrix metalloproteinase genes MMP2 and MMP14, which are substrates of PCs, in 30 matched pairs of samples of human lung cancer tumor and adjacent tissues without pathology. Significant changes in the expression of PCs have been revealed in tumor tissues: increased FURIN mRNA level (p<0.00005) and decreased mRNA levels of PCSK2 (p<0.007), PCSK5 (p<0.0002), PCSK7 (p<0.002), PCSK9 (p<0.00008), and MBTPS1 (p<0.00004) as well as a tendency to increase in the level of PCSK1 mRNA. Four distinct groups of samples have been identified by cluster analysis of the expression patterns of PC genes in tumor vs. normal tissue. Three of these groups covering 80% of samples feature a strong elevation in the expression of a single gene in cancer: FURIN, PCSK1, or PCSK6. Thus, the changes in the expression of PC genes have a limited number of scenarios, which may reflect different pathways of tumor development and cryptic features of tumors. This finding allows to consider the mRNAs of PC genes as potentially important tumor markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cluster Analysis
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics*
  • Proprotein Convertases / genetics*

Substances

  • Proprotein Convertases

Grants and funding

This work was supported in part by the Program of the Russian Academy of Sciences for Molecular and Cell Biology, the Program of the Russian Academy of Sciences “Fundamental Science for Medicine”, Russian Foundation for Basic Research (project nos. 12-04-00961 and 12-04-01438), the Federal Program “R&D in Priority Directions of the Russian Scientific-Technological Complex Development in 2007–2012” (state contracts 02.522.11.2005 and 16.512.12.2002), the Federal Program “The development of pharmaceutical and medical industry in the Russian Federation until 2020 and beyond” (state contract 11411.1008700.13.084), and a grant of the President of Russian Federation for Scientific Schools (no. 5638.2010.4). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.