Co-expression Network Analysis Identifies Fourteen Hub Genes Associated with Prognosis in Clear Cell Renal Cell Carcinoma

Curr Med Sci. 2020 Aug;40(4):773-785. doi: 10.1007/s11596-020-2245-6. Epub 2020 Aug 29.

Abstract

Renal cancer is a common genitourinary malignance, of which clear cell renal cell carcinoma (ccRCC) has high aggressiveness and leads to most cancer-related deaths. Identification of sensitive and reliable biomarkers for predicting tumorigenesis and progression has great significance in guiding the diagnosis and treatment of ccRCC. Here, we identified 2397 common differentially expressed genes (DEGs) using paired normal and tumor ccRCC tissues from GSE53757 and The Cancer Genome Atlas (TCGA). Then, we performed weighted gene co-expression network analysis and protein-protein interaction network analysis, 17 candidate hub genes were identified. These candidate hub genes were further validated in GSE36895 and Oncomine database and 14 real hub genes were identified. All the hub genes were up-regulated and significantly positively correlated with pathological stage and histologic grade of ccRCC. Survival analysis showed that the higher expression level of each hub gene tended to predict a worse clinical outcome. ROC analysis showed that all the hub genes can accurately distinguish between tumor and normal samples, and between early stage and advanced stage ccRCC. Moreover, all the hub genes were positively associated with distant metastasis, lymph node infiltration, tumor recurrence and the expression of MKi67, suggesting these genes might promote tumor proliferation, invasion and metastasis. Furthermore, the functional annotation demonstrated that most genes were enriched in cell-cycle related biological function. In summary, our study identified 14 potential biomarkers for predicting tumorigenesis and progression, which might contribute to early diagnosis, prognosis prediction and therapeutic intervention.

Keywords: bioinformatics; biomarker; clear cell renal cell carcinoma; weighted gene co-expression network analysis.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Renal Cell / diagnosis*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology
  • Disease Progression
  • Early Detection of Cancer
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Kidney Neoplasms / diagnosis*
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Protein Interaction Maps
  • Survival Analysis
  • Up-Regulation*

Substances

  • Biomarkers, Tumor