GCN2 is a potential prognostic biomarker for human papillary renal cell carcinoma

Cancer Biomark. 2018;22(3):395-403. doi: 10.3233/CBM-170922.

Abstract

Postoperative recurrence for papillary renal cell carcinoma (PRCC) remains a tough problem in clinic. Previous studies have shown that general control nonderepressible kinase 2 (GCN2) was critically involved in tumour development. However, its function and clinical significance in renal cancer remain unknown. In this study, we investigated the role of GCN2 in PRCC. GCN2 silencing suppressed the viability and proliferation, promoted apoptosis of renal cancer cells. We found that the protein level of GCN2 was increased in PRCC tissues. Immunohistochemistry was performed in 84 patients with PRCC to explore the association of GCN2 level with clinical significance. High GCN2 protein level was observed to be significantly correlated with adverse clinicopathological parameters, such as larger tumor size, higher TNM stage, higher Fuhurman Grade, and lymph node metastasis. We evaluated patient outcomes according to various clinical parameters as well as GCN2 expression by Kaplan-Meier curves. Multivariate analysis revealed that GCN2 overexpression can be a predictive factor correlated with reduced OS and PFS of postoperative PRCC patients. Collectively, GCN2 is potentially to play crucial roles in PRCC progression, and its overexpression may be used to predict poor prognosis and promising therapeutic strategy for PRCC patients.

Keywords: GCN2; PRCC; overall survival; prognosis; progression free survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / genetics
  • Biomarkers, Tumor*
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / metabolism
  • Carcinoma, Papillary / mortality*
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / mortality*
  • Cell Survival / genetics
  • Female
  • Gene Expression
  • Gene Knockdown Techniques
  • Gene Silencing
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Young Adult

Substances

  • Biomarkers, Tumor
  • EIF2AK4 protein, human
  • Protein Serine-Threonine Kinases