| 摘要: |
| 通过构建结肠癌坏死性凋亡相关lncRNA的预后模型,进行肿瘤细胞免疫浸润分析,并筛选结肠癌潜在的治疗药物,为结肠癌患者的免疫治疗提供理论基础。从TCGA数据库中下载并整理结肠癌病人的表达和临床数据,提取坏死性凋亡基因的表达量,通过共表达和单因素Cox分析预测结肠癌坏死性凋亡相关的lncRNA。使用LASSO回归分析构建包含11个坏死性凋亡相关lncRNA的预后模型,并通过生存分析、ROC曲线、单因素和多因素Cox分析,Nomogram,列线图和校准曲线来验证模型的准确性,通过GSEA富集分析找到高低风险组中活跃的代谢通路,进一步进行免疫分析并筛选治疗结肠癌的潜在药物；高低风险组中活跃的代谢通路与免疫关系密切,且高风险组病人具有更高的免疫浸润水平,在HAVCR2(TIM3),LAG3,PDCD1LG2(PD-L2) 和IDO1等免疫检查点中表现出良好的活性,并且对免疫治疗药物更敏感；本研究获得的11个坏死性凋亡相关lncRNA可为结肠癌治疗的深入研究提供理论依据,获得的lncRNA免疫检查点抑制剂和瑞卡帕布、伊利斯莫、长春花碱、帕纳替尼、奥拉帕尼、来那度胺、尼洛替尼等20种药物可为结肠癌的免疫治疗和潜在药物的确定提供较好的理论基础。 |
| 关键词: 结肠癌 坏死性凋亡 lncRNA 药物筛选 |
| DOI：10.12113/202307002 |
| 分类号:Q344+.14 |
| 文献标识码:A |
| 基金项目:德州学院博士科研基金项目(No.2019xgrc25). |
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| Necroptosis-related lncRNA for model construction and drug screening in colon cancer |
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LIU Yanling, TAN Liwen
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(College of Medicine and Nursing, Dezhou University, Dezhou 253023, Shandong, China)
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| Abstract: |
| To construct a prognostic model for lncRNA related to necrotic apoptosis in colon cancer, This paper conducts tumor cell immune infiltration analysis, and screens potential therapeutic drugs for colon cancer, providing a theoretical basis for immunotherapy in colon cancer patients. The expression gene and clinical data of colon cancer patients are downloaded from the TCGA database to extract the levels of necroptosis-related genes, and then is used to predict the necroptosis-related lncRNAs of colon cancer by co-expression and Cox univariate analysis. A prognostic model containing 11 necroptosis-related lncRNAs is constructed using LASSO regression analysis. And the accuracy of the model is verified by survival analysis, ROC curve, univariate and multivariate Cox analysis, nomogram, and calibration curve.Through GSEA enrichment analysis, active metabolic pathways are identified in the high and low risk Groups. And immunoassay is conducted and potential drugs for colon cancer are screened.The active pathways in the high and low risk groups are closely related to immunity. And it is found that patients in the high group have higher levels of immune infiltration, exhibiting good activity in immune checkpoints such as HAVCR2(TIM3), LAG3, PDCD1LG2(PD-L2) and IDO1, and are more sensitive to immunotherapy drugs. 11 lncRNAs related to necrotic apoptosis obtained in this study can provide a theoretical basis for in-depth research on the treatment of colon cancer. The lncRNA immune checkpoint inhibitors and 20 drugs for AG.014699,Elesclomol,Vinblastine,AP.24534,AZD.2281,Lenalidomide,Nilotinib obtained can provide a good theoretical basis for the immunotherapy of colon cancer and the determination of potential drugs. |
| Key words: Colon cancer Necrotizing apoptosis LncRNA Drug screening |
