High expression of P2X7R is an independent postoperative indicator of poor prognosis in colorectal cancer

Hum Pathol. 2017 Jun:64:61-68. doi: 10.1016/j.humpath.2017.03.019. Epub 2017 Apr 12.

Abstract

The purinergic P2X7 receptor (P2X7R) is a master regulator of inflammation and inflammation-related diseases. Recently, P2X7R has been reportedly involved in carcinogenesis and tumor progression. In this study, we investigated the expression pattern and prognostic merit of P2X7R in human colorectal cancer (CRC). The expression profile of P2X7R in 12 pairs of CRC and non-tumorous specimens was evaluated using Western blotting analysis. Additionally, we performed immunohistochemistry (IHC) on 116 paraffin-embedded CRC specimens, and evaluated the correlation between P2X7R expression and clinicopathological factors. P2X7R was overexpressed in CRC samples, compared with adjacent non-tumorous ones. High P2X7R expression significantly correlated with tumor size (P = .0177), Lymph node metastasis (P = .0128), and TNM stage (P = .0081). Furthermore, univariate and multivariate Cox regression analyses revealed that P2X7R expression could serve as an independent prognostic factor for poor overall survival (P = .0197). Treatment with P2X7R agonist BzATP led to the activation of Akt and NF-κB pathways. Consequently, we revealed that BzATP accelerated the proliferation of CRC cells, whereas co-incubation with PI3K/Akt inhibitor LY294002 significantly impaired BzATP-induced proliferation of CRC cells. Our findings implied that P2X7R may serve as a valuable prognostic indicator and promising therapeutic target of CRC.

Keywords: Colorectal cancer; Metastasis; P2X7R; Prognosis; Proliferation.

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Biopsy
  • Blotting, Western
  • Cell Proliferation
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • Female
  • HCT116 Cells
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Purinergic P2X Receptor Agonists / pharmacology
  • Receptors, Purinergic P2X7 / drug effects
  • Receptors, Purinergic P2X7 / metabolism*
  • Risk Factors
  • Signal Transduction
  • Time Factors
  • Transcription Factor RelA / metabolism
  • Tumor Burden

Substances

  • Biomarkers, Tumor
  • P2RX7 protein, human
  • Protein Kinase Inhibitors
  • Purinergic P2X Receptor Agonists
  • RELA protein, human
  • Receptors, Purinergic P2X7
  • Transcription Factor RelA
  • Proto-Oncogene Proteins c-akt