基于生物信息学分析LIX1基因在前列腺癌中的表达与免疫浸润的关系

Expression and Immune Infiltration of LIX1 in Prostate Cancer Based on Bioinformatics

摘要: 目的：探讨肢体和中枢神经系统表达因子1 (Limb and CNS expressed 1, LIX1)在前列腺癌(prostate cancer, PCa)中的表达及临床意义。方法：利用Oncomine和UALCAN数据库分析LIX1在PCa组织中的表达；利用R3.6.3软件绘制受试者工作特征曲线(Receiver Operating Characteristic curve，ROC曲线)和临床基线表，分析LIX1表达与PCa患者临床特征参数的关系；应用CANCERTOOL、GEPIA和TIMEER数据库分析LIX1表达水平与PCa患者预后及其与免疫细胞浸润的关系。利用LinkedOmics数据库筛选LIX1共表达基因及进行GSEA分析，探讨LIX1在PCa中潜在作用的信号通路。结果：LIX1 mRNA在PCa组织中表达水平显著降低且对PCa的诊断具有一定准确性。LIX1表达水平与PCa患者的TNM分期、Gleason分期、年龄和PSA水平显著负相关。LIX1低表达患者预后不佳，具有更高的复发风险。LIX1表达水平与PCa巨噬细胞的浸润水平呈正相关。LIX1及其共表达的基因主要富集在线粒体呼吸链复合物的组装，胞质分裂，核糖体和细胞周期途径等信号通路。结论：LIX1在PCa中表达降低，且与免疫浸润有关，可作为PCa诊断和不良预后的新型标志物。

Abstract: Objective: To reveal the expression and clinical features of Limb and CNS expressed 1 (LIX1) in prostate cancer (PCa). Methods: We used Oncomine and UALCAN databases to analyze the expres-sion of LIX1 in PCa. The Receiver Operating Characteristic curve (ROC) and baseline clinical charac-teristics of LIX1 were plotted by R3.6.3 package, and the relationship between LIX1 expression and clinical characteristics of PCa patients was also identified. Then, we applied CANCERTOOL, GEPIA and TIMEER databases to explore the expression and clinical outcomes, and the correlation with immune infiltration of LIX1 in PCa. Meanwhile, LinkedOmics database was used to identify co-expression genes of LIX1, and then we performed the Gene Set Enrichment Analysis (GSEA) to explore the potential signaling pathway. Results: The expression level of LIX1 in PCa tissues was significantly reduced and the diagnosis of PCa was accurate. The expression level of LIX1 was signif-icantly negatively correlated with PCa patients’ TNM grade, Gleason scores, age and PAS level. Low LIX1 had worsened disease-free survival and a higher risk of recurrence of PCa patients, and was positive related to the abundance of macrophages. GSEA suggests that LIX1 genes are mainly con-centrated in mitochondria respiratory chain complex assembly, cytokinesis, ribosomes and cell cy-cle pathways. Conclusion: The expression of LIX1 is decreased in PCa and is associated with immune infiltration, which can be used as a novel marker for PCa diagnosis and poor prognosis.