Objective  To investigate the expression level of pyrimidinergic receptor P2Y6 (P2RY6) and its clinical implications in patients with non-small cell lung cancer (NSCLC).

  Methods  We obtained the gene expression profiles and clinical datasets of patients with NSCLC, lung squamous cell carcinoma, and lung adenocarcinoma from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data bases. A nonparametric test was used to analyze the differences in P2RY6 expression levels between cancer tissues and adjacent normal tissues. Immunohistochemistry was performed to investigate the expression of P2RY6 in lung squamous cell carcinoma or lung adenocarcinoma and adjacent normal tissues. A Chi-square test was applied to validate any correlations between P2RY6 expression levels and the clinical features of patients with lung squamous cell carcinoma and lung adenocarcinoma. Furthermore, the relationship between P2RY6 expression and overall or progression-free survival (PFS) was evaluated using the KaplanMeier method and Log-rank tests. Finally, a Cox proportional hazard regression model was applied to appraise the predictive ability of P2RY6 expression levels for the survival of patients with lung squamous cell carcinoma.

  Results  P2RY6 was abundantly expressed in NSCLC, lung adenocarcinoma, and lung squamous cell carcinoma tissues. Among patients with lung adenocarcinoma, a high expression level of P2RY6 was associated with sex but not survival. Among patients with lung squamous cell carcinoma showing high expression levels of P2RY6, both overall survival (OS) and PFS were short. This suggests that high expression levels of P2RY6 may be a new independent risk factor for survival in patients with lung squamous cell carcinoma.

  Conclusions  P2RY6 is associated with the survival of patients with lung squamous cell carcinoma. A high expression level of P2RY6 indicates shorter OS and PFS and may be a novel independent risk factor for survival in patients with lung squamous cell carcinoma.