TFIIB-related factor 2 over expression is a prognosis marker for early-stage non-small cell lung cancer correlated with tumor angiogenesis

PLoS One. 2014 Feb 11;9(2):e88032. doi: 10.1371/journal.pone.0088032. eCollection 2014.

Abstract

Background: The aim of this study was to examine BRF2 expression in patients with non-small cell lung cancer (NSCLC) and explore the relationship of BRF2 protein with clinicopathologic factors, tumor angiogenesis and prognosis.

Methods: Both BRF2 protein and intratumoral microvessels were examined by immunohistochemical staining in 107 non-small cell lung cancer patients. Intratumoral microvessel density (MVD) was measured by counting CD-34 positive immunostained endothelial cells. Western blot and RT-PCR analyses were utilized to investigate the BRF2 expression status in tissues.

Results: A notably higher level of BRF2 expression was found in NSCLC tissues at protein levels. In addition, univariate and multivariate analysis demonstrated that BRF2 protein over-expression and high MVD were significantly associated with tumor relapse. Although BRF2 overexpression and high MVD indicated poor 5-year overall survival (p = 0.004 and p = 0.019, respectively), multivariate analysis demonstrated that only BRF2 overexpression was an independent prognostic factor for unfavorable overall survival (P = 0.021).

Conclusions: BRF2 is a promising biomarker to identify individuals with poor prognostic potential and a possible target for anti-angiogenic therapy for patients with early-stage NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD34 / metabolism
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Male
  • Microcirculation
  • Middle Aged
  • Multivariate Analysis
  • Neovascularization, Pathologic*
  • Prognosis
  • Recurrence
  • Transcription Factor TFIIIB / genetics*
  • Transcription Factor TFIIIB / metabolism*
  • Treatment Outcome

Substances

  • Antigens, CD34
  • BRF2 protein, human
  • Biomarkers, Tumor
  • Transcription Factor TFIIIB

Grants and funding

Project supported by the National Natural Science Foundation of China (No. 30571844), and the Science and Technology Development Foundation of Shandong Province (No. 2009GG10002007), and the National Natural Science Foundation of Shandong Province (No. ZR2009CM090), and the Wu Jie Ping Foundation (No. 320.6750.12393). Sponsors had no involvement in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. The funders had no role in study design, data collection and analysis.