A four-gene signature predicts survival in clear-cell renal-cell carcinoma

Oncotarget. 2016 Dec 13;7(50):82712-82726. doi: 10.18632/oncotarget.12631.

Abstract

Clear-cell renal-cell carcinoma (ccRCC) is the most common pathological subtype of renal cell carcinoma (RCC), accounting for about 80% of RCC. In order to find potential prognostic biomarkers in ccRCC, we presented a four-gene signature to evaluate the prognosis of ccRCC. SurvExpress and immunohistochemical (IHC) staining of tissue microarrays were used to analyze the association between the four genes and the prognosis of ccRCC. Data from TCGA dataset revealed a prognostic prompt function of the four genes (PTEN, PIK3C2A, ITPA and BCL3). Further discovery suggested that the four-gene signature predicted survival better than any of the four genes alone. Moreover, IHC staining demonstrated a consistent result with TCGA, indicating that the signature was an independent prognostic factor of survival in ccRCC. Univariate and multivariate Cox proportional hazard regression analysis were conducted to verify the association of clinicopathological variables and the four genes' expression levels with survival. The results further testified that the risk (four-gene signature) was an independent prognostic factors of both Overall Survival (OS) and Disease-free Survival (DFS) (P<0.05). In conclusion, the four-gene signature was correlated with the survival of ccRCC, and therefore, may help to provide significant clinical implications for predicting the prognosis of patients.

Keywords: bioinformatics; ccRCC; gene signature; prognosis; tissue microarray.

MeSH terms

  • B-Cell Lymphoma 3 Protein
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Renal Cell / chemistry
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / therapy
  • Databases, Genetic
  • Female
  • Gene Expression Profiling / methods*
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / chemistry
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / therapy
  • Male
  • Middle Aged
  • PTEN Phosphohydrolase / genetics
  • Phenotype
  • Phosphatidylinositol 3-Kinases / genetics
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins / genetics
  • Pyrophosphatases / genetics
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Tissue Array Analysis
  • Transcription Factors / genetics
  • Transcriptome*

Substances

  • B-Cell Lymphoma 3 Protein
  • BCL3 protein, human
  • Biomarkers, Tumor
  • Proto-Oncogene Proteins
  • Transcription Factors
  • PIK3C2A protein, human
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Pyrophosphatases
  • ITPA protein, human