泛癌症分析揭示HIV诱导IL-6的表达对多种癌症的潜在预后影响和机制研究

Revelation of the potential prognostic effects and mechanisms of IL-6 expression induced by HIV on multiple cancers via pan-cancer analysis

目的:通过泛癌症分析来揭示人类免疫缺陷病毒(HIV)诱导白细胞介素-6(IL-6)的表达对不同类型肿瘤潜在预后的影响,并研究其免疫学机制。方法:将THP-1细胞分为对照组和HIV-1感染组,采用实时荧光定量PCR(RT-qPCR)法检测IL-6在两组中的表达水平;通过从cBioPortal和癌症基因组图谱(TCGA)数据库下载33种的10688个样本癌症的基因表达数据和临床数据,分析IL-6在泛癌症中的表达水平,采用COX回归分析检验IL-6基因表达与每种癌症类型患者生存的相关性;使用xCell Web服务器分析33种癌症类型的免疫细胞丰度并进行相关性分析。结果:与对照组相比,在12 h、24 h时,HIV-1感染组IL-6表达水平升高(P<0.05)。公共数据库整合分析结果显示,IL-6在不同癌症类型中有明显的差异表达,生存分析结果提示IL-6的表达与癌症患者的生存时间显著相关。xCell Web服务器分析结果显示,HIV诱导的IL-6表达水平可能通过调节Th1、Th2等免疫效应细胞的激活而特异性地影响肿瘤微环境,导致不同的预后。结论:IL-6在不同类型肿瘤组织中的表达和功能具有高度的异质性,HIV诱导IL-6的高表达可能导致感染HIV的不同癌症类型患者的不同预后,对艾滋病合并肿瘤患者的治疗和预后预测有着重要意义。

Objective:To reveal the prognostic effects and immunological mechanisms of interleukin-6(IL-6)expression induced by human immunodeficiency virus(HIV)across diverse tumor types via pan-cancer analysis.Methods:THP-1 cells were divided into the control group and the HIV-1 infected group,and the expression level of IL-6 in the two groups was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Gene expression data and clinical data of 10,688 cancer samples from 33 types of cancer were downloaded from cBioPortal and Cancer Genome Atlas(TCGA)databases to analyze the expression level of IL-6 in pan-cancer and COX regression analysis was performed to test the correlation between gene expression level of IL-6 and survival of patients with each cancer type.The abundance of immune cells in 33 cancer types was analyzed using the xCell Web server and correlations were analyzed.Results:Compared with the control group,IL-6 expression level in HIV-1 infected group was increased at 12 h and 24 h(P<0.05).Public database integration analysis showed that IL-6 was significantly differentially expressed in different cancer types.Survival analysis indicated that the expression of IL-6 was significantly correlated with the survival time of patients with cancers.Moreover,the xCell Web server analysis showed that the expression level of IL-6 induced by HIV might specifically affect the cancer microenvironment by regulating the activation of immune effector cells such as Th1 and Th2,leading to different prognosis.Conclusion:The expression and function of IL-6 in different types of cancer tissues are highly heterogeneous.High expression of IL-6 induced by HIV may lead to different prognosis of HIV-infected patients with different types of cancer,which is of great significance for the treatment and prognosis prediction of AIDS patients with cancer.