概要
目的
开发一种基于趋化因子信号通路的多基因模型, 可以有效预测结直肠癌患者的总生存期和治疗反应.
创新点
结直肠癌具有高度异质性, 迫切需要开发可靠的标志物用于预测患者的预后和治疗效果. 研究显示趋化因子信号通路关键基因表达变化与结直肠癌转移和预后密切相关, 但尚缺乏基于该信号通路的基因模型用来预测患者的临床预后. 本研究基于趋化因子信号通路构建了一种新的多基因模型 (CSbMgSig), 用于结直肠癌患者的预后风险分层和总体生存时间预测, 为结直肠癌患者的治疗提供指导.
方法
首先, 考虑到转移对结直肠癌预后的重要影响, 我们在原发和转移性结直肠癌样本中鉴定了差异表达的趋化因子信号通路相关基因. 然后, 结合单因素 Cox 回归分析和 LASSO Cox 回归分析建立基于趋化因子信号通路的预后模型 CSbMgSig, 并在另一个独立数据集通过 Kaplan-Meier 生存分析和时间依赖性受试者工作特征 (ROC) 分析进一步验证其预后性能. 此外, 我们还进行了基因本体 (GO) 富集分析、 基因集富集分析 (GSEA)、 单样本基因集富集分析 (ssGSEA) 和化疗反应分析, 以探索 CSbMgSig 在结直肠癌致病机制中的功能及其对免疫浸润和化疗反应的影响.
结论
构建的由 8 个趋化因子信号通路相关基因组成的预后模型 CSbMgSig, 可以有效地在训练集和验证集中区分高危结直肠癌患者, 并被证明是总生存期的独立预测因子. 功能分析结果表明, 该特征在结直肠癌患者的免疫浸润和对药物的反应中起关键作用. 因此, 基于趋化因子信号通路的多基因模型 CSbMgSig 是一种很有前景的工具, 可以进行风险分层、 生存预测和治疗评估, 从而有利于结直肠癌患者的个性化管理.
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Acknowledgments
This work was supported by the National Natural Science Foundation of China (Nos. 31900490 and 31770903) and the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (No. 19KJB180027).
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Xin QI designed the research and drafted the manuscript. Xin QI, Donghui YAN, Jiachen ZUO, and Rui WANG collected the data and performed the computational analyses. Xin QI, Donghui YAN, Jiachen ZUO, Rui WANG, and Jiajia CHEN revised the manuscript. All authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Xin QI, Donghui YAN, Jiachen ZUO, Rui WANG, and Jiajia CHEN declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
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Detailed methods are provided in the electronic supplementary materials of this paper.
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Materials and methods; Figs. S1–S5
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Development of a novel chemokine signaling-based multigene signature to predict prognosis and therapeutic response in colorectal cancer
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Qi, X., Yan, D., Zuo, J. et al. Development of a novel chemokine signaling-based multigene signature to predict prognosis and therapeutic response in colorectal cancer. J. Zhejiang Univ. Sci. B 22, 1053–1059 (2021). https://doi.org/10.1631/jzus.B2100412
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DOI: https://doi.org/10.1631/jzus.B2100412