Identification of HIPK3 as a potential biomarker and an inhibitor of clear cell renal cell carcinoma

Aging (Albany NY). 2021 Jan 20;13(3):3536-3553. doi: 10.18632/aging.202294. Epub 2021 Jan 20.

Abstract

Invasion and metastasis are the main causes of poor prognosis in patients with clear cell renal cell carcinoma (ccRCC). The homeodomain interacting protein kinases (HIPKs) can regulate cell proliferation and apoptosis. Little is known about the prognostic role of HIPKs in ccRCC. Here we use Kaplan-Meier survival analysis and multivariate analysis to analyze the correlation of overall survival (OS) and disease-free survival (DFS). ROC curves analyzed the relationship between clinicopathological parameters and HIPK3 expression in ccRCC. Univariate analysis and multivariate analysis confirmed that the expression of HIPK3 was associated with OS (HR, 0.701; P=0.041) and DFS (HR, 0.630; P=0.012). Low HIPK3 expression was a poor prognostic factor and HIPK3 expression was significantly down-regulated in ccRCC cancer tissues when compared with normal renal tissues. In vitro cell results also confirmed that HIPK3 over-expression could inhibit tumor growth and malignant characteristics. The results indicate that low expression of HIPK3 in ccRCC tissues is significantly associated with poor survival rates in tumor patients, and HIPK3 may be used as a valuable biomarker and inhibitor of ccRCC.

Keywords: HIPK3; biomarker; ccRCC; prognostic indicator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / genetics
  • Disease-Free Survival
  • Down-Regulation
  • Female
  • Gene Knock-In Techniques
  • Humans
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Survival Rate

Substances

  • Intracellular Signaling Peptides and Proteins
  • HIPK3 protein, human
  • Protein Serine-Threonine Kinases