嘌呤能受体X1与肺腺癌预后及免疫细胞浸润的相关性研究

目的：探索嘌呤能受体X1(purinergic receptor，P2RX1)与肺腺癌(LUAD)患者预后及免疫细胞浸润的相关性。方法：利用生物信息学技术分析非小细胞肺癌中P2RX1的表达及其甲基化与患者预后的关系，对P2RX1共表达基因进行富集分析并筛选核心基因。利用TIMER 2.0数据库、R软件等分析P2RX1与免疫细胞、免疫检查点、免疫基质评分等的相关性。结果：P2RX1在LUAD中表达下调，低表达P2RX1的患者预后较差(P<0.05)，且P2RX1与肿瘤纯度、分期等临床病理因素有关(P<0.05)。P2RX1的表达与肺鳞癌患者预后无明显相关。Cg06475633等P2RX1 CpG位点甲基化与患者预后相关。P2RX1共表达基因主要富集于免疫细胞活化、分化等通路和生物学进程，核心基因主要包括BTK、IKZF1等。P2RX1的表达与B细胞浸润、免疫/基质评分、PD-1、CTLA-4等多个免疫检查点显著相关(P<0.05)。结论：P2RX1有望成为LUAD诊断和免疫治疗的新靶点。

Correlations among P2RX1,prognosis and immune cells infiltration in lung adenocarcinoma

OBJECTIVE: To explore the expression level of P2RX1 in non-small cell lung adenocarcinoma (LUAD) and to investigate relationships among P2RX1 expression,prognosis and tumor immune infiltration level of LUAD patients.METHODS: Different bioinformatic tools were used to explore correlations between P2RX1 expressions and DNA methylation levels in LUAD.The correlations between P2RX1 expression and prognosis of LUAD patients was also explored by different tools.The P2RX1 co-expressed genes were screened to explore the functional classifications and to select hub genes in LUAD.TIMER 2.0 database,R software and other bioinformatic tools were used to investigate correlations among P2RX1 expression,immune infiltration and immune checkpoints in LUAD.RESULTS: P2RX1 expressions were significantly downregulated in LUAD (P<0.05).Low P2RX1 expression levels tended to present worse prognosis in LUAD patients.In LUAD,P2RX1 expression was correlated with many clinicopathological factors such as tumor purity,stage and so on (P<0.05).No significant relationship was found between P2RX1 expression and prognosis of cancer.The methylation level of Cg06475633 was significantly associated with prognosis in LUAD patients.The P2RX1 coexpressed genes were mainly involved in immune cells activation,differentiation and other molecular biological process and signaling pathways.The selected hub genes contained BTK,IKZF1 and others.Most Hub genes were correlated with better prognosis in LUAD.The expression of P2RX1 was significantly correlated with immune cells infiltration especially with B cells infiltration in LUAD.P2RX1 expression was also positively correlated with immune stromal score,PD-1,CTLA-4 and many other immune checkpoints in LUAD (P< 0.05).CONCLUSION: P2RX1 might be useful as a biomarker for detection and as a therapeutic target for LUAD.