Immunological role and clinical prognostic significance of P2RY6 in lung adenocarcinoma: a multi-omics studies and single-cell sequencing analysis

Abstract

Background There is increasing evidence that recombinant human P2Y purinoceptor 6 (P2RY6) may be involved in inflammatory responses. However, the role of P2RY6 in lung adenocarcinoma (LUAD) remains unknown. Methods We used transcriptomic, genomic, single-cell transcriptomic, and methylation sequencing data from The Cancer Genome Atlas database to analyze the aberrant status and prognostic value of P2RY6 in a variety of tumors. The LUAD single-cell sequencing dataset was used to explore the effect of P2RY6 on the tumor microenvironment. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was used to quantify immune cells in the tumor microenvironment. We also analyzed the correlation of P2RY6 with immune checkpoints and immune regulation-related genes. The correlation of between tumor mutation burden (TMB), microsatellite instability (MSI), and P2RY6 expression was also analyzed simultaneously. Tissue microarray and immunohistochemistry were employed to assess the expression of P2RY6 in internal tumor samples. Results Our findings indicate that P2RY6 exhibits significantly higher expression levels in various cancer tissues, particularly in LUAD. High expression of P2RY6 was closely associated with a poor prognosis for patients, and it plays a role in regulating immune-related pathways, such as cytokine-cytokine receptor interaction. Notably, P2RY6 expression is closely linked to the abundance of CD8 + T cells. Furthermore, we have developed a P2RY6-related inflammation prediction model that demonstrates promising results in predicting the prognosis of LUAD patients, with an AUC (area under the curve) value of 0.83. This performance is significantly better than the traditional TNM staging system. Through single-cell transcriptome sequencing analysis, we observed that high P2RY6 expression is associated with increased intercellular communication. Additionally, pathway enrichment analysis revealed that P2RY6 influences antigen presentation and processing pathways within the LUAD microenvironment. Conclusions This study suggests that P2RY6 would be a new target for immunotherapy in LUAD.

Prognostic prediction using a gene signature developed based on exhausted T cells for liver cancer patients

“…However, PIP4K2A could also act as a tumor promoter in tumor progression, and knockdown of PIP4K2A alone significantly increases the proliferation of cancer cells [ 71 ]. P2Y purinoceptor 6 (P2RY6) is high-expressed in many cancer tissues, which is associated with poor prognosis [ 72 ]. A high level of P2RY6 promotes the formation of a tumor-promoting microenvironment through enhancing resistance to apoptosis [ 73 ], while blocking Wnt/β-catenin and Hippo/YAP signaling pathways in P2RY6-deficient mice could inhibit skin tumorigenesis [ 74 ].…”