基于免疫基因相关的结直肠癌预后模型的构建分析及药物筛选OA北大核心CSTPCD
The construction of a prognostic model for colorectal cancer based on immune gene correlation and drug screening
目的 寻找新的生物标志物预测结直肠癌(CRC)患者的预后.方法 利用单因素Cox回归分析和最小绝对收缩和选择算子(LASSO)回归分析,从癌症基因组图谱(TC-GA)数据库中建立了一个免疫相关基因的结直肠癌预后模型.通过利用表达数据估算恶性肿瘤组织中的基质细胞和免疫细胞(ESTIMATE)软件包以及通过估算RNA转录本的相对子集识别细胞类型(CIBERSORT)软件包比较了高低风险组患者的免疫浸润特征.此外,还分析了不同风险组患者的免疫检查点的表达水平.通过癌症药物敏感性基因组学(GDSC)数据库比较了两个风险组患者对化疗药物的敏感性.结果 结果显示,基于免疫基因构建的预后模型可以较好地预测CRC患者的总体生存期(OS),结果显示1年、3年和5年OS的曲线下与坐标轴面积(AUC)值分别为0.764(95%CI:0.751~0.793)、0.773(95%CI:0.761~0.779)和0.760(95%CI:0.742~0.774).低风险组患者的免疫检查点表达水平更高和免疫细胞更丰富如T细胞(P<0.001)、树突状细胞(P<0.001)、巨噬细胞(P<0.001)、中性粒细胞(P<0.001).高风险组患者可能对于阿昔替尼、伊马替尼、甲氨蝶呤、帕唑帕尼、雷帕霉素、舒尼替尼和他普西加金等一些化疗药物更敏感.结论 基于19个免疫基因的预后模型能够有效的预测CRC患者的预后.不同患者中免疫微环境中的免疫细胞数量和活跃程度可能是影响其对免疫检查抑制剂和化疗药物响应的重要因素.
Objective To search for new biomarkers to predict prognosis in colorectal cancer (CRC) patients.Methods A prognostic model was developed for colorectal cancer with immune-related genes from the cancer ge-nome atlas (TCGA) database using one-way Cox regression analysis and least absolute shrinkage and selection op-erator (LASSO) regression analysis.Moreover, the immune infiltration characteristics of patients in high and low risk groups was compared by sstimation of stromal and immune cells in malignant tumor tissues using expression da-ta (ESTIMATE) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) .In addition, the expression levels of immune checkpoints were analyzed in patients from different risk groups.The sen-sitivity of patients in the two risk groups to chemotherapeutic agents was also compared based on genomics of drug sensitivity in cancer (GDSC).Results It was found that the prognostic model constructed based on immune genes could better predict the overall survival (OS) of CRC patients,and the results showed area under curve (AUC) values of 0.764 (95% CI:0.751-0.793), 0.773 (95% CI:0.761 -0.779), and 0.760 (95% CI:0.742 -0.774) for 1-, 3-, and 5-year OS, respectively.Patients in the low-risk group had higher expression levels of im-mune checkpoints and more abundant immune cells such as T cells (P<0.001) , dendritic cells (P<0.001) , macrophages (P<0.001) , neutrophils (P<0.001) .Patients in the high-risk group might be more sensitive to some chemotherapeutic agents such as axitinib, imatinib, methotrexate, pazopanib, rapamycin, sunitinib and tasig-arnib.Conclusion A prognostic model based on 19 immune genes was effective in predicting the prognosis of CRC patients.The number and activity of immune cells in the immune microenvironment in different patients may be an important factor influencing their response to immunocheck inhibitors and chemotherapeutic agents.
郑伟;赵佳佳;程祥;谭泓鑫;黄琦
安徽医科大学第二附属医院肿瘤科,合肥 230601安徽医科大学第二附属医院神经外科,合肥 230601
临床医学
结直肠癌免疫检查点抑制剂肿瘤微环境预后模型免疫相关基因
colorectal cancerimmune checkpoint inhibitorstumour microenvironmentprognostic modelsimmune-related genes
《安徽医科大学学报》 2024 (005)
789-796 / 8
国家自然科学基金(编号:82003037);安徽省转化医学研究院科研基金(编号:2022zhyx-C79)
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