胰腺癌免疫相关预后生物标志物的鉴定

Xiaodong Lin, Jiakang Ma, Kaikai Ren, M. Hou, B. Zhou, Yong Shen, Ling Zhang, Ling Yuan, Jun Ma
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引用次数: 0

摘要

癌症(PC)的免疫治疗面临重大挑战。寻找免疫相关基因进行靶向治疗是当务之急。我们旨在通过多种综合免疫富集分析方法鉴定免疫相关信使核糖核酸(mRNAs),以预测PC的存活率。PC基因组学和临床数据从TCGA下载。我们使用ssGSEA分析了29个免疫细胞的相对富集,并将PC样品分为三个免疫渗透亚组。免疫细胞浸润水平和途径通过估计数据和KEGG进行评估。独立危险因素来源于WGCNA、LASSO回归和Cox回归分析的联合分析。根据四种信使核糖核酸计算免疫风险评分,以确定其在预测生存率方面的价值。PPI分析用于分析基因之间的联系和潜在途径。最后,将PC样品分为三个免疫渗透亚组。免疫高亚群具有较高的免疫评分、免疫细胞浸润性、HLA/PD-L1表达水平、免疫相关通路富集性和较好的生存能力。鉴定了四个潜在的预后免疫相关基因(ITGB7、RAC2、DNASE1L3和TRAF1)。免疫风险评分可能是一个具有高灵敏度和特异性的潜在生存预测指标(AUC值=0.708,HR=1.445)。生成了一个具有7个节点和5个潜在靶向通路的PPI网络。总之,我们通过用ssGSEA算法计算基质细胞和免疫细胞的富集来估计PC肿瘤微环境中免疫浸润的状态,并确定了四个影响免疫细胞浸润在肿瘤微环境的比例和分布的预后免疫相关基因。为成为PC个体治疗的重要免疫靶点奠定了理论基础。
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Identification of Immune-Related Prognostic Biomarkers in Pancreatic Cancer
Immunotherapy for pancreatic cancer (PC) faces significant challenges. It is urgent to find immunerelated genes for targeted therapy. We aimed to identify immune-related messenger ribonucleic acids (mRNAs) with multiple methods of comprehensive immunoenrichment analysis in predicting survival of PC. PC genomics and clinical data were downloaded from TCGA. We analyzed relative enrichment of 29 immune cells using ssGSEA and classified PC samples into three immuneinfiltrating subgroups. Immune cell infiltration level and pathways were evaluated by ESTIMATE data and KEGG. Independent risk factors were derived from the combined analysis of WGCNA, LASSO regression and Cox regression analyses. Immune risk score was calculated according to four mRNAs to identify its value in predicting survival. PPI analysis was used to analyze the connections and potential pathways among genes. Finally, PC samples were classified into three immuneinfiltrating subgroups. Immunity high subgroup had higher immune score, soakage of immune cells, HLA/PD-L1 expression level, immune-related pathways enrichment and better survivability. Four potential prognostic immune-related genes (ITGB7, RAC2, DNASE1L3, and TRAF1) were identified. Immune risk score could be a potential survival prediction indictor with high sensitivity and specificity (AUC values = 0.708, HR = 1.445). A PPI network with seven nodes and five potential targeted pathways were generated. In conclusion, we estimated the state of immune infiltration in the PC tumor microenvironment by calculating stromal and immune cells enrichment with ssGSEA algorithms, and identified four prognostic immune-related genes that affect the proportion and distribution of immune cells infiltration in the tumor microenvironment. They lay a theoretical foundation to be important immunity targets of individual treatment in PC.
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来源期刊
Nanoscience and Nanotechnology Letters
Nanoscience and Nanotechnology Letters Physical, Chemical & Earth Sciences-MATERIALS SCIENCE, MULTIDISCIPLINARY
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审稿时长
2.6 months
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