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

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.

• Authors: Yi Qing, Qing Li, Tao Ren, Wei Xia, Yu Peng, Gao-Lei Liu, Hao Luo, Yu-Xin Yang, Xiao-Yan Dai, Shu-Feng Zhou, Dong Wang
• Journal: Drug design, development and therapy (Drug Des Devel Ther) Vol. 9 Pg. 901-9 ( 2015) ISSN: 1177-8881 [Electronic] New Zealand
• PMID: 25733810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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