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肝细胞癌中具有免疫抑制作用的预后相关氧化应激模型的鉴定

Identification of Prognosis-Related Oxidative Stress Model with Immunosuppression in HCC.

作者信息

Ren Zhixuan, Zhang Jiakang, Zheng Dayong, Luo Yue, Song Zhenghui, Chen Fengsheng, Li Aimin, Liu Xinhui

机构信息

Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China.

Cancer Center, Southern Medical University, Guangzhou 510315, China.

出版信息

Biomedicines. 2023 Feb 24;11(3):695. doi: 10.3390/biomedicines11030695.

Abstract

For hepatocellular carcinoma (HCC) patients, we attempted to establish a new oxidative stress (OS)-related prognostic model for predicting prognosis, exploring immune microenvironment, and predicting the immunotherapy response. Significantly differently expressed oxidative stress-related genes (DEOSGs) between normal and HCC samples from the Cancer Genome Atlas (TCGA) were screened, and then based on weighted gene coexpression network analysis (WGCNA), HCC-related hub genes were discovered. Based on the least absolute shrinkage and selection operator (LASSO) and cox regression analysis, a prognostic model was developed. We validated the prognostic model's predictive power using an external validation cohort: the International Cancer Genome Consortium (ICGC).Then a nomogram was determined. Furthermore, we also examined the relationship of the risk model and clinical characteristics as well as immune microenvironment. 434 DEOSGs, comprising 62 downregulated and 372 upregulated genes ( < 0.05 and |log2FC| ≥ 1), and 257 HCC-related hub genes were recognized in HCC. Afterward, we built a five-DEOSG (, , , , and ) prognostic risk model. Using the nomogram, the risk model was shown to have good prognostic value. Compared to the low risk group, HCC patients with high risk had poorer outcomes, worse pathological grades, and advanced tumor stages ( < 0.05). There were significant increases in , , , and expression in HCC samples, while expression was decreased. Finally, Real-time PCR (RT-qPCR) confirmed the mRNA expressions of five genes (, , , , ) in HCC cell lines. Our study constructed a prognostic OS-related model with strong predictive power and potential as an immunosuppressive biomarker for HCC leading to improving prediction and providing new insights for HCC immunotherapy.

摘要

对于肝细胞癌(HCC)患者,我们试图建立一种新的氧化应激(OS)相关预后模型,用于预测预后、探索免疫微环境以及预测免疫治疗反应。我们筛选了来自癌症基因组图谱(TCGA)的正常样本与HCC样本之间显著差异表达的氧化应激相关基因(DEOSGs),然后基于加权基因共表达网络分析(WGCNA)发现了HCC相关的枢纽基因。基于最小绝对收缩和选择算子(LASSO)及Cox回归分析,开发了一种预后模型。我们使用外部验证队列:国际癌症基因组联盟(ICGC)验证了该预后模型的预测能力。然后确定了列线图。此外,我们还研究了风险模型与临床特征以及免疫微环境的关系。在HCC中识别出434个DEOSGs,包括62个下调基因和372个上调基因(<0.05且|log2FC|≥1),以及257个HCC相关枢纽基因。随后,我们构建了一个包含五个DEOSG(,,,,和)的预后风险模型。使用列线图显示该风险模型具有良好的预后价值。与低风险组相比,高风险的HCC患者预后较差、病理分级更差且肿瘤分期更晚(<0.05)。HCC样本中的,,,和表达显著增加,而表达降低。最后,实时定量聚合酶链反应(RT-qPCR)证实了五个基因(,,,,)在HCC细胞系中的mRNA表达。我们的研究构建了一种具有强大预测能力的预后OS相关模型,有潜力作为HCC的免疫抑制生物标志物,从而改善预测并为HCC免疫治疗提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dd8/10045103/d29c44b3aabd/biomedicines-11-00695-g001.jpg

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