Comprehensive analysis of P2Y family genes expression, immune characteristics, and prognosis in pan-cancer

Chuan Liu; Xiaoli Wang; Siwei Wang; Jiankang Xiang; Huabing Xie; Zongbiao Tan; Xinshu Li; Jixiang Zhang; Weiguo Dong

doi:10.1016/j.tranon.2023.101776

Comprehensive analysis of P2Y family genes expression, immune characteristics, and prognosis in pan-cancer

Transl Oncol. 2023 Nov:37:101776. doi: 10.1016/j.tranon.2023.101776. Epub 2023 Sep 4.

Authors

Chuan Liu¹, Xiaoli Wang², Siwei Wang³, Jiankang Xiang¹, Huabing Xie⁴, Zongbiao Tan¹, Xinshu Li⁵, Jixiang Zhang¹, Weiguo Dong⁶

Affiliations

¹ Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
² Department of Plastic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.
³ Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
⁴ Department of General Practice, Renmin Hospital of Wuhan University, Wuhan 430060, China.
⁵ Department of Clinical Medicine, Xi'an Medical of University, Xi'an 710068, China.
⁶ Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address: dongweiguo@whu.edu.cn.

Abstract

Background: P2Y receptors are a family of G protein-coupled receptor genes that have an important function in cancer development and metastasis. However, systematic studies have not been conducted on human tumors. This study attempted to explore the role of P2Y family genes (P2Ys) in pan-cancer.

Methods: Gene expression and clinical data were downloaded from The Cancer Genome Alas dataset. Gene differential expression, mutation, prognosis, tumor microenvironment (TME) (containing immune cells infiltration, Estimate/immune/stromal scores, immune checkpoints, immune and molecular subtypes, DNA repair genes and methyltransferase), clinical correlation, protein-protein interaction network and functional enrichment analysis were performed. In addition, experiments such as western blots were performed for validation.

Results: Eight P2Ys were differentially expressed in most tumor and normal tissues, and their abnormal expression in a variety of cancers could significantly reduce the survival rate of patients. Expression levels of P2Ys, especially P2Y6, P2Y12, P2Y13, P2Y14, were correlated significantly with immune cells, immune checkpoint genes, immune and molecular subtypes and Estimate/immune/stromal scores in a variety of cancers such as uveal melanoma, liver hepatocellular carcinoma, stomach adenocarcinoma, colorectal cancer (CRC), prostate adenocarcinoma, breast invasive carcinoma and uterine corpus endometrial carcinoma (all p < 0.05). P2Ys play an important role in TME and are involved in immune regulation. In addition, enrichment analysis and western blots showed that the levels of P2Y2 and P2Y6 expression regulate the Akt/GSK-3β/β-catenin pathway in CRC, thereby affecting epithelial-to-mesenchymal transition.

Conclusion: P2Ys may be used as potential pan-cancer biomarkers in prognosis and immunology. They may also be new targets for tumor immunotherapy, which has wide clinical implications.

Keywords: Bioinformatics analysis; Immune infiltration; P2Y; Pan-cancer; Prognosis.