Expression and prognosis analyses of the Tob/BTG antiproliferative (APRO) protein family in human cancers

PLoS One. 2017 Sep 18;12(9):e0184902. doi: 10.1371/journal.pone.0184902. eCollection 2017.

Abstract

Background: Despite advances in early diagnosis and treatment, cancer remains the major cause of mortality in the world. The Tob/BTG antiproliferative (APRO) protein family is reported to participate in diverse human diseases. However, there's little known about their expression and prognostic values in most human cancers.

Methods: We performed a detailed cancer vs. normal analysis. The mRNA expression levels of APRO family in various cancers were analyzed via the Oncomine database. Moreover, the Kaplan-Meier Plotter and PrognScan databases were used to evaluate the prognostic values.

Results: We observed that the mRNA expression levels of TOB1-2 and BTG2 were decreased in most cancers compared with normal tissues, while BTG3 was upregulated in most cancers. In survival analyses based on Kaplan-Meier Plotter, TOB1, BTG1 and BTG4 showed significant associations with survival outcome of different subtypes of breast cancer. Decreased BTG2 was related with poor relapse free survival (RFS) in all subtypes of breast cancer. Especially, besides RFS, reduced BTG2 also indicated worse overall survival and distant metastasis free survival in breast cancer patients who were classified as luminal A. Significant prognostic effects of the whole APRO family were also found in lung adenocarcinoma, but not in squamous cell lung carcinoma. In addition, potential correlations between some APRO family members and survival outcomes were also observed in ovarian, colorectal and brain cancer.

Conclusions: Some members of APRO family showed significant expression differences between cancer and normal tissues, and could be prognostic biomarkers for defined cancer types.

MeSH terms

  • Cell Cycle Proteins / biosynthesis*
  • Cell Cycle Proteins / genetics
  • Cell Proliferation*
  • Databases, Genetic*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Neoplasm Metastasis
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / mortality*
  • Survival Rate

Substances

  • Cell Cycle Proteins
  • Neoplasm Proteins

Grants and funding

This work was supported by the National Natural Science Foundation of China under Grant number 81370484 (Na Liu). The funder had been greatly helpful in study design, decision to publish, and modification of the manuscript.