Upregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric cancer

Drug Des Devel Ther. 2015 Feb 16:9:901-9. doi: 10.2147/DDDT.S75152. eCollection 2015.

Abstract

Introduction: Gastric cancer is a fatal malignancy with a rising incidence rate. Effective methods for early diagnosis, monitoring metastasis, and prognosis are currently unavailable for gastric cancer. In this study, we examined the association of programmed death ligand-1 (PD-L1) and apurinic/apyrimidinic endonuclease 1 (APE1) expression with the prognosis of gastric cancer.

Methods: The expressions of PD-L1 and APE1 were detected by immunohistochemistry in 107 cases of human gastric carcinoma. The correlation of PD-L1 and APE1 expression with the clinicopathologic features of gastric carcinoma was analyzed by SPSS version 19.0.

Results: The positive expression rates of PD-L1 and APE1 in gastric cancer tissues were 50.5% (54/107) and 86.9% (93/107), respectively. PD-L1 and APE1 positive expressions were significantly associated with depth of invasion, lymph node metastasis, pathological type, overall survival, and higher T stage. Furthermore, the expression of PD-L1 in highly differentiated gastric cancers was higher than that in poorly differentiated cancers (P=0.008). Moreover, the expression of APE1 and PD-L1 in gastric cancers was positively correlated (r=0.336, P<0.01). Multivariate analysis showed that the depth of invasion was a significant prognostic factor (risk ratio 19.91; P=0.000), but there was no significant relationship with PD-L1, APE1, prognosis, and other characteristics.

Conclusion: The deregulation of PD-L1 and APE1 might contribute to the development and the poor prognosis of gastric cancer. Our findings suggest that high expression of PD-L1 and APE1 is a risk factor of gastric cancer and a new biomarker to predict the prognosis of gastric cancer. Furthermore, our findings suggest that targeting the PD-L1 and APE1 signaling pathways may be a new strategy for cancer immune therapy and targeted therapy for gastric cancer, especially in patients with deep invasion and lymph node metastasis.

Keywords: gastric carcinoma; immunohistochemistry; potential targets; prognostic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / biosynthesis
  • B7-H1 Antigen / metabolism*
  • Carcinogenesis / metabolism*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / biosynthesis
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Prognosis
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Up-Regulation

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • APEX1 protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase