Rationale: The characterization of new theranostic biomarkers is crucial to improving the clinical outcome of patients with advanced lung cancer. Here, we aimed at characterizing the P2RX7 receptor, a positive modulator of the anti-tumor immune response, in patients with lung adenocarcinoma./nMethods: The expression of P2RX7 and its splice variants was analyzed by RT-qPCR using areas of tumor and non-tumor lung adenocarcinoma (LUAD) tissues on both immune and non-immune cells. The biological activity of P2RX7 was studied by flow cytometry using fluorescent dyes. Bi-molecular fluorescence complementation and confocal microscopy were used to assess the oligomerization of P2RX7. Tumor immune infiltrates were characterized by immunohistochemistry./nResults: Fifty-three patients with LUAD were evaluated. P2RX7A, and 3 alternative splice variants were expressed in LUAD tissues and expression was down regulated in tumor versus adjacent non-tumor tissues. The protein retained biological activity only in immune cells. The P2RX7B splice variant was differentially upregulated in immune cells (P < 0.001) of the tumor and strong evidence of oligomerization of P2RX7A and B was observed in the HEK expression model, which correlated with a default in the activity of P2RX7. Finally, LUAD patients with a high level of P2RX7B had non-inflamed tumors (P = 0.001)./nConclusion: Our findings identified P2RX7B as a new theranostic tool to restore functional P2RX7 activity and open alternative therapeutic opportunities to improve LUAD patient outcome.

中文翻译：

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P2RX7B是肺腺癌患者的新型治疗诊断标志物

理由：新的治疗诊断生物标志物的表征对于改善晚期肺癌患者的临床结局至关重要。在此，我们旨在表征肺腺癌患者中P2RX7受体（一种抗肿瘤免疫应答的正调节剂）。/n方法：利用RT-qPCR使用肿瘤和肿瘤区域分析P2RX7及其剪接变体的表达。免疫和非免疫细胞上的非肿瘤性肺腺癌（LUAD）组织。通过使用荧光染料的流式细胞术研究了P2RX7的生物学活性。双分子荧光互补和共聚焦显微镜用于评估P2RX7的寡聚。肿瘤免疫浸润的特点是免疫组织化学法。评价了53名LUAD患者。P2RX7A和3个其他剪接变体在LUAD组织中表达，并且与相邻的非肿瘤组织相比，其表达下调。该蛋白质仅在免疫细胞中保留生物学活性。所述P2RX7B剪接变体中的免疫细胞（被差分上调P肿瘤的<0.001）和P2RX7A和B在HEK表达模型，该模型与P2RX7活性的默认相关观察的低聚的有力证据。最后，LUAD患者中高水平的P2RX7B患有非炎症性肿瘤（P = 0.001）。 我们的发现确定P2RX7B是恢复功能性P2RX7活性并打开替代治疗机会以改善LUAD患者预后的新的治疗方法。