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Journal of Zhejiang University SCIENCE B
ISSN 1673-1581(Print), 1862-1783(Online), Monthly
2021 Vol.22 No.12 P.1053-1059
Development of a novel chemokine signaling-based multigene signature to predict prognosis and therapeutic response in colorectal cancer
Abstract: Colorectal cancer (CRC) is the most lethal gastrointestinal cancer in both males and females worldwide (Sung et al., 2021). Because of the high heterogeneity of tumors, robust prognostic biomarkers are urgently needed in CRC management (Koncina et al., 2020). Chemokine signaling is a well-known pivotal player in immunity, inflammation, and cancer metastasis (Lacalle et al., 2017; Poeta et al., 2019; Do et al., 2020), and multiple genes involved in chemokine signaling have been demonstrated as potential prognostic biomarkers for CRC (Cabrero-De Las Heras and Martínez-Balibrea, 2018; Ottaiano et al., 2020; Yu et al., 2020). Therefore, the aim of our study was to develop a chemokine signaling-based multigene signature (CSbMgSig) that could effectively predict overall survival (OS) and therapeutic response for patients with CRC.
Key words: Chemokine signaling; Multigene signature; Colorectal cancer; Prognosis; Therapeutic response
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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DOI:
10.1631/jzus.B2100412
CLC number:
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On-line Access:
2021-12-14
Received:
2021-05-09
Revision Accepted:
2021-08-16
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