摘要
肠道微生物组在人体的免疫反应、能量代谢、癌症发生中发挥着重要作用.长链非编码RNA(Long Non-coding RNAs,lncRNAs)的差异表达通常与肿瘤的发生、转移、预后和耐药性密切相关.然而,人们对于肠道微生物相关的lncRNAs与胃癌之间的关系知之甚少.本研究通过癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库获取胃癌组织和癌旁组织的转录组数据和临床数据.皮尔森相关分析(|coefficients|>0.4,and p<0.001)用于识别肠道微生物组相关的lncRNAs.单因素Cox回归,LASSO(Least Absolute Shrinkage and Selection Operator)回归算法和多因素Cox回归用于构建肠道微生物组相关lncRNAs的风险预测模型.通过3个肠道微生物组相关lncRNAs(AC093627.7,AL139147.1,AC083902.1)构建了风险模型.本研究采用K-M生存曲线和受试者工作特征(Receiver Operating Characteristics,ROC)曲线来验证和评估风险模型.此外,论文还构建了列线图用于预测患者的预后.基因本体论(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集用于分析肠道微生物组高低风险组间潜在的生物功能和通路差异.最后,分析了肠道微生物组高低风险组间的免疫特征,免疫表观评分(Immunophenoscore,IPS),微卫星不稳定性(Microsatellite Instability,MSI),肿瘤突变负荷(Tumor Mutation Burden,TMB)和免疫治疗药物敏感性差异.MSI和TMB分析都表明肠道微生物组低风险组的胃癌患者更可能从免疫检查点抑制剂治疗中获益,这说明肠道微生物组在调控宿主的免疫反应中发挥作用,有潜力成为免疫检查点治疗的生物标志物之一.
The gut microbiome plays an important role in host immune response,energy metabolism,and carcinogenesis.Differential expression of long non-coding RNAs(lncRNAs)is often associated with tumorigenesis,metastasis,prognosis,and drug resistance.However,little is known about the relationship between gut microbiome-associated lncRNAs and gastric cancer.We obtained transcriptome and clinical data of gastric cancer and normal tissues through The Cancer Genome Atlas(TCGA)database.Pearson correlation analysis(|coefficients|0.4,and p0.001)was used to identify gut microbiome-associated lncRNAs.Univariate Cox regression,least absolute shrinkage and selection operator(LASSO)Cox regression,and multivariate Cox regression were used to construct a risk prediction model of gut microbiome-associated lncRNAs.The risk models constructed by three gut microbiome-associated lncRNAs(AC093627.7,AL139147.1,AC083902.1)were in excellent agreement with the predicted results.Next,Kaplan-Meier analysis and time-dependent receiver operating characteristic(ROC)were used to validate and evaluate the risk characteristics.The nomogram was constructed to predict patient prognosis.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were employed to investigate potential biological functions and pathway differences between high-and low-risk groups of gut microbiome.Finally,we also analyzed immune characteristics,immunophenoscore(IPS),microsatellite instability(MSI),tumor mutation burden(TMB),and immunotherapy drug sensitivity differences between high-and low-risk groups of the gut microbiome.Interestingly,both MSI and TMB analyses indicated that gastric cancer patients in the low-risk group were more likely to benefit from immune checkpoint inhibitor therapy,suggesting that the gut microbiome plays a key role in modulating host immunity and has the potential as one of the biomarkers for immune checkpoint therapy.
作者
王振
张乐
刘虹汝
张钰哲
WANG Zhen;ZHANG Le;LIU Hongru;ZHANG Yuzhe(School of Basic Medicine,Dali University,Dali 671000,Yunnan,China)
出处
《昆明理工大学学报（自然科学版）》
北大核心
2023年第5期140-153,231,共15页
Journal of Kunming University of Science and Technology(Natural Science)
基金
云南省滇西抗病原植物资源筛选研究重点实验室开放项目(APKL2101)
大理大学博士科研启动基金项目(KYBS2018012)
云南省地方高校联合专项面上项目(202001BA070001-064,202101BA070001-102)
云南省教育厅科学研究基金项目(2023Y0950,2022Y80)。
