目的：累积的证据突出了氧化应激在结肠癌（CRC）的肿瘤形成和进展中的生物学意义。我们的研究旨在建立一个可靠的氧化应激相关签名以预测患者的临床结果和治疗反应。 方法：从公共数据集中回顾性分析CRC患者的转录组数据和临床特征。使用LASSO分析构建氧化应激相关签名以预测总生存期、无病生存期、疾病特异性生存期和无进展生存期。此外，通过TIP、CIBERSORT、oncoPredict等方法分析不同风险子集之间的抗肿瘤免疫力、药物敏感性、信号通路和分子亚型。该签名中的基因分别在人类结肠黏膜细胞系（FHC）和CRC细胞系（SW-480和HCT-116）中通过RT-qPCR或Western blot进行实验验证。 结果：建立了一个氧化应激相关签名，由ACOX1、CPT2、NAT2、NRG1、PPARGC1A、CDKN2A、CRYAB、NGFR和UCN组成。该签名具有出色的生存预测能力，并与较差的临床病理特征相关联。此外，该签名与抗肿瘤免疫力、药物敏感性和CRC相关通路相关。在分子亚型中，CSC亚型的风险评分最高。实验表明，CRC中的CDKN2A和UCN上调，而ACOX1、CPT2、NAT2、NRG1、PPARGC1A、CRYAB和NGFR下调。在H2O2诱导的CRC细胞中，它们的表达明显改变。 结论：总之，我们的发现构建了一个氧化应激相关签名，可以预测CRC患者的生存预后和治疗反应，从而有助于预后预测和辅助治疗决策。版权所有©2023 Cao、Chen、Gu、Wang和Xu。

Objective: Accumulated evidence highlights the biological significance of oxidative stress in tumorigenicity and progression of colorectal cancer (CRC). Our study aimed to establish a reliable oxidative stress-related signature to predict patients' clinical outcomes and therapeutic responses. Methods: Transcriptome profiles and clinical features of CRC patients were retrospectively analyzed from public datasets. LASSO analysis was used to construct an oxidative stress-related signature to predict overall survival, disease-free survival, disease-specific survival, and progression-free survival. Additionally, antitumor immunity, drug sensitivity, signaling pathways, and molecular subtypes were analyzed between different risk subsets through TIP, CIBERSORT, oncoPredict, etc. approaches. The genes in the signature were experimentally verified in the human colorectal mucosal cell line (FHC) along with CRC cell lines (SW-480 and HCT-116) through RT-qPCR or Western blot. Results: An oxidative stress-related signature was established, composed of ACOX1, CPT2, NAT2, NRG1, PPARGC1A, CDKN2A, CRYAB, NGFR, and UCN. The signature displayed an excellent capacity for survival prediction and was linked to worse clinicopathological features. Moreover, the signature correlated with antitumor immunity, drug sensitivity, and CRC-related pathways. Among molecular subtypes, the CSC subtype had the highest risk score. Experiments demonstrated that CDKN2A and UCN were up-regulated and ACOX1, CPT2, NAT2, NRG1, PPARGC1A, CRYAB, and NGFR were down-regulated in CRC than normal cells. In H2O2-induced CRC cells, their expression was notably altered. Conclusion: Altogether, our findings constructed an oxidative stress-related signature that can predict survival outcomes and therapeutic response in CRC patients, thus potentially assisting prognosis prediction and adjuvant therapy decisions.Copyright © 2023 Cao, Chen, Gu, Wang and Xu.