Pyrimidinergic receptor P2Y6 expression is elevated in lung adenocarcinoma and is associated with poor prognosis

Article type: Research Article

Authors: Wang, Xiuli^{a; 1} | Zhao, Baoshan^{a; 1} | Ren, Dan^{b; 1} | Hu, Xiaolei^a | Qiao, Juanjuan^a | Zhang, Dongmei^a | Zhang, Yanzhi^a | Pan, Yu^c | Fan, Yuhua^a | Liu, Lili^a | Wang, Xiaoxue^a | Ma, Huanhuan^a | Jia, Xueling^a | Song, Sihang^d | Zhao, Chong^e | Liu, Jingbo^b | Wang, Lin^{a; *}

Affiliations: [a] Department of Pathology and Pathophysiology, Harbin Medical University-Daqing, Daqing, Heilongjiang, China | [b] Department of Pathology, Daqing Longnan Hospital, Daqing, Heilongjiang, China | [c] Department of Anatomy, Harbin Medical University-Daqing, Daqing, Heilongjiang, China | [d] Department of Histology and Embryology, Harbin Medical University-Daqing, Daqing, Heilongjiang, China | [e] Library of Harbin Medical University-Daqing, Daqing, Heilongjiang, China

Correspondence: [*] Correspondence author: Lin Wang, Department of Pathology and Pathophysiology, Harbin Medical University-Daqing, No.39 Xinyang Road, Hi-Tech Zone, Daqing 163319, Heilongjiang, China. E-mail: wanglin@hmudq.edu.cn.

Note: [1] These authors contributed equally.

Abstract: BACKGROUD: Previous in vitro studies have indicated that pyrimidinergic receptor P2Y6 (P2RY6, P2Y6 receptor) may function as a cancer-promoting factor in lung adenocarcinoma (LUAD). However, the prognostic significance of P2RY6 expression in LUAD has not been investigated. OBJECTIVE: This study aimed to assess the impact of P2RY6 expression on the survival of patients with LUAD. METHODS: First, we assessed P2RY6 mRNA and protein expression in LUAD and non-cancerous lung tissues using the online bioinformatics analysis tool GEPIA, fresh LUAD tissues, and LUAD tissue microarrays (TMAs). Second, we investigated the correlation between P2RY6 expression and clinicopathological parameters of LUAD patients based on data from The Cancer Genome Atlas (TCGA) database and TMAs. Finally, we analyzed the prognostic significance of P2RY6 expression in LUAD using the online survival analysis tool Kaplan-Meier Plotter and data from TMAs. RESULTS: We demonstrated that P2RY6 mRNA and protein expression levels in LUAD tissues were significantly higher than those in non-cancerous lung tissues. The expression of P2RY6 in LUAD was positively correlated with poor differentiation, more lymph node metastasis, and more advanced clinical stage. Higher P2RY6 expression level was correlated with shorter survival of the LUAD patients. Univariate and multivariate Cox regression analyses indicated that higher P2RY6 tumor expression was an independent unfavorable prognostic factor for LUAD patients. CONCLUSIONS:P2RY6 expression was elevated in LUAD and correlated with poor prognosis.

Keywords: Lung adenocarcinoma, purinergic signaling, pyrimidinergic receptor P2Y6, prognosis

DOI: 10.3233/CBM-230137

Journal: Cancer Biomarkers, vol. 38, no. 2, pp. 191-201, 2023