Department of Pneumology, Yiwu Central Hospital, Zhejiang, China.
World J Surg Oncol. 2023 Oct 26;21(1):341. doi: 10.1186/s12957-023-03216-1.
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.
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.
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.
This study suggests that P2RY6 would be a new target for immunotherapy in LUAD.
越来越多的证据表明，重组人 P2Y 嘌呤能受体 6（P2RY6）可能参与炎症反应。然而，P2RY6 在肺腺癌（LUAD）中的作用尚不清楚。
我们使用来自癌症基因组图谱数据库的转录组、基因组、单细胞转录组和甲基化测序数据，分析 P2RY6 在多种肿瘤中的异常状态和预后价值。使用 LUAD 单细胞测序数据集来探索 P2RY6 对肿瘤微环境的影响。通过估计相对 RNA 转录物子集（CIBERSORT）进行细胞类型鉴定，用于量化肿瘤微环境中的免疫细胞。我们还分析了 P2RY6 与免疫检查点和免疫调节相关基因的相关性。同时分析了肿瘤突变负担（TMB）、微卫星不稳定性（MSI）和 P2RY6 表达之间的相关性。还使用组织微阵列和免疫组织化学评估了内部肿瘤样本中 P2RY6 的表达。
我们的研究结果表明，P2RY6 在各种癌症组织中表达水平显著升高，尤其是在 LUAD 中。高表达 P2RY6 与患者预后不良密切相关，并且在调节免疫相关途径（如细胞因子-细胞因子受体相互作用）方面发挥作用。值得注意的是，P2RY6 表达与 CD8+T 细胞的丰度密切相关。此外，我们开发了一种基于 P2RY6 的炎症预测模型，该模型在预测 LUAD 患者的预后方面表现出良好的效果，AUC（曲线下面积）值为 0.83。这一表现明显优于传统的 TNM 分期系统。通过单细胞转录组测序分析，我们观察到高 P2RY6 表达与细胞间通讯增加有关。此外，通路富集分析表明，P2RY6 影响 LUAD 微环境中的抗原呈递和加工途径。
本研究表明，P2RY6 可能成为 LUAD 免疫治疗的新靶点。
