肾透明细胞癌中m7G相关长链非编码RNAs与肿瘤微环境及免疫治疗的关系  

Comprehensive analysis of m7G-associated lncRNAs with tumor microenvironment as well as immunotherapy in renal clear cell carcinoma

作　　者：朱丽君 王彩霞 石韶华 Zhu Lijun;Wang Caixia;Shi Shaohua(Department of Kidney Transplantation and Dialysis Center,Second People′s Hospital of Shanxi Province,Taiyuan,Shanxi 030012,China)

机构地区：[1]山西省第二人民医院肾移植透析中心,山西太原030012

出　　处：《中国药物与临床》2025年第3期185-191,I0001-I0006,共13页Chinese Remedies & Clinics

摘　　要：目的分析N7-甲基鸟嘌呤(N7-methylguanosine,m7G)相关的长链非编码RNA(long non-coding RNA,lncRNA)在肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)中的作用。方法从癌症基因图谱(the cancer genome atlas,TCGA)数据库中检索ccRCC患者的信息,筛选出m7G相关的lncRNA,基于m7G相关lncRNA的预后特征(m7G-related lncRNA prognostic signatures,m7G-LPSs)建模。分析肿瘤微环境(tumor microenvironment,TME)、功能富集、免疫检查点与m7G相关lncRNA的关系。采用IMvigor 210队列、肿瘤突变负荷(tumor mutation burden,TMB)和pRRophetic包比较免疫治疗反应。结果在共表达研究中,筛选出8个可能的预后标志,在高危人群中上调AC112721.2、AC020907.4、AC009948.1、CEROX1、AC110015.1和下调RAP2C-AS1、AC079760.1、RPL34-DT。ccRCC的预后特征与不同的免疫信号通路、免疫侵袭和免疫检查点密切相关,高危患者预后较差,与CD4^(+)T细胞和CD8^(+)T细胞呈正相关,免疫评分和肿瘤细胞均较高。CTLA4、TIGIT、PDCD1和LAG3免疫检查点在不同风险组之间差异有统计学意义,CTLA4与AC112721.2、AC020907.4、AC079760.1、AC009948.1和AC110015.1呈正相关,与CEROX1呈负相关,不同的免疫药物在高危和低危患者间有不同的反应。结论构建了一个基于ccRCC中m7G相关lncRNA的预后风险模型,为ccRCC的发病机制和治疗提供新思路。Objective To investigate the role of N7-methylguanosine(m7G)-related long noncoding RNA(lncRNA)in clear cell renal cell carcinoma(ccRCC).Methods Data on ccRCC patients were retrieved from the cancer genome atlas(TCGA)database,containing transcriptome and clinical information.After extracting the expression of the m7G genes and lncRNAs,m7G-related lncRNAs were derived using correlation analysis.The prognosis of ccRCC was modeled using Lasso regression based on m7G-related lncRNA prognostic signatures(m7G-LPSs).Then we utilized GSEA,ssGSEA,estimate,and limma algorithms to identify tumor microenvironment and functional enrichment among different risk groups,as well as the relationship between immune checkpoints and m7G-related lncRNA.Then we employed IMvigor 210 cohort,TMB,and pRRophetic to compare the immunotherapy response.Results In coexpression study,we discovered that lncRNA expression and m7G level were highly associated.Eight m7G-related lncRNAs were identified as prognostic signatures,including which were upregulated(AC112721.2,AC020907.4,AC009948.1,CEROX1,and AC110015.1)and which were downregulated(RAP2C-AS1,AC079760.1,and RPL34-DT)in high-risk groups.Our prognostic signatures were strongly associated with different tumor-/immune-signaling pathways,immune invasion,and immune checkpoints.Patients with higher risk had a worse prognosis,with a positive correlation of CD4^(+)T/CD8^(+)T cells,along with higher estimate and immune scores,as well as greater tumor cell purity.Immune checkpoints differ considerably across risk groups,including CTLA4,TIGIT,PDCD1,and LAG3.CTLA4 was shown to be favorably connected to AC112721.2,AC020907.4,AC079760.1,AC009948.1 and AC110015.1,while negatively related to CEROX1.Different immunotherapeutic drugs showed different sensitive response between high-/low-risk patients.Conclusion A prognostic risk model based on m7G related lncRNAs in ccRCC has been constructed,providing new insights into the pathogenesis and treatment of ccRCC.

关 键 词：肾透明细胞癌 m7G lncRNA 肿瘤微环境 免疫疗法 

分 类 号：R737.11[医药卫生—肿瘤]