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一种用于识别弥漫性大B细胞淋巴瘤低氧亚型的新型低氧特征基因预后模型。

A Novel Hypoxia-Featured Genes Prognostic Model for Identification of Hypoxia Subtypes in Diffuse Large B-Cell Lymphoma.

作者信息

Lyu Geng, Sun Ruixin, Liu Xiaxin, Xu Zizhen

机构信息

Department of Laboratory Medicine, College of Health Science and Technology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine, Ruijin Hospital affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Cell Biochem Biophys. 2025 Jun;83(2):2265-2279. doi: 10.1007/s12013-024-01637-7. Epub 2024 Dec 11.

Abstract

Diffuse large B-cell lymphoma (DLBCL), known as the predominant type of aggressive B-cell lymphoma, is biologically and clinically heterogeneous. The prognosis of DLBCL is quite different among subtypes. Hypoxia is one of the key elements in tumor microenvironment, promoting tumor progression by means of various mechanisms, such as increased proliferation, altered metabolism, enhanced angiogenesis, and greater migratory capability, among others. The primary purpose of this research is to investigate the connection between hypoxia-featured genes (HFGs), prognosis in DLBCL, and their capacity association with the immune microenvironment. Various hypoxia-associated patterns for DLBCL patients from GEO and TCGA databases were identified by means of an unsupervised consensus clustering algorithm. CIBERSORT and IOBR package is used to identify different immune infiltration status. To develop a predictive model using hypoxia-related genes, we conducted univariate Cox regression, multivariate Cox regression, and LASSO regression assessment. Subsequently, we confirmed the predictive importance of these hypoxia-associated genes, highlighting hypoxia-associated characteristics, and explored the connection between the hypoxia model and the immune environment. Three hypoxia clusters were identified. We also observed that each pattern of hypoxia response was significantly related to different prognoses. It was found that the immune status among hypoxia clusters is different. After developing a prognostic risk model using 5 hypoxia-related genes, we discovered that the risk score is related to immune factors and how effective drugs are in treating DLBCL. In DLBCL patients, varying hypoxia patterns correlate with both prognostic outcomes and the immune microenvironment. Hypoxia-featured genes (HFGs) function as a standalone predictive element in these patients. It is also potentially a reliable indicator for predicting clinical responses to ICI therapy and traditional drugs.

摘要

弥漫性大B细胞淋巴瘤(DLBCL)是侵袭性B细胞淋巴瘤的主要类型,在生物学和临床上具有异质性。DLBCL各亚型的预后差异很大。缺氧是肿瘤微环境中的关键因素之一,通过多种机制促进肿瘤进展,如增加增殖、改变代谢、增强血管生成和提高迁移能力等。本研究的主要目的是探讨缺氧特征基因(HFGs)与DLBCL预后之间的联系,以及它们与免疫微环境的能力关联。通过无监督一致性聚类算法,从GEO和TCGA数据库中识别出DLBCL患者的各种缺氧相关模式。使用CIBERSORT和IOBR软件包来识别不同的免疫浸润状态。为了利用缺氧相关基因建立预测模型,我们进行了单变量Cox回归、多变量Cox回归和LASSO回归评估。随后,我们证实了这些缺氧相关基因的预测重要性,突出了缺氧相关特征,并探讨了缺氧模型与免疫环境之间的联系。识别出三个缺氧簇。我们还观察到,每种缺氧反应模式都与不同的预后显著相关。发现缺氧簇之间的免疫状态不同。在使用5个缺氧相关基因建立预后风险模型后,我们发现风险评分与免疫因素以及药物治疗DLBCL的效果有关。在DLBCL患者中,不同的缺氧模式与预后结果和免疫微环境均相关。缺氧特征基因(HFGs)在这些患者中作为独立的预测因素发挥作用。它也可能是预测ICI治疗和传统药物临床反应的可靠指标。

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