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代谢组学和转录组学分析确定了胸腺上皮肿瘤中的重要基因。

Metabolomic and Transcriptomic Profiling Identified Significant Genes in Thymic Epithelial Tumor.

作者信息

Tang Enyu, Zhou Yang, Liu Siyang, Zhang Zhiming, Zhang Rixin, Huang Dejing, Gao Tong, Zhang Tianze, Xu Guangquan

机构信息

Department of Thoracic Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.

Department of Cardiac Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.

出版信息

Metabolites. 2022 Jun 20;12(6):567. doi: 10.3390/metabo12060567.

Abstract

Thymomas and thymic carcinomas are malignant thymic epithelial tumors (TETs) with poor outcomes if non-resectable. However, the tumorigenesis, especially the metabolic mechanisms involved, is poorly studied. Untargeted metabolomics analysis was utilized to screen for differential metabolic profiles between thymic cancerous tissues and adjunct noncancerous tissues. Combined with transcriptomic data, we comprehensively evaluated the metabolic patterns of TETs. Metabolic scores were constructed to quantify the metabolic patterns of individual tumors. Subsequent investigation of distinct clinical outcomes and the immune landscape associated with the metabolic scores was conducted. Two distinct metabolic patterns and differential metabolic scores were identified between TETs, which were enriched in a variety of biological pathways and correlated with clinical outcomes. In particular, a high metabolic score was highly associated with poorer survival outcomes and immunosuppressive status. More importantly, the expression of two prognostic genes (ASNS and BLVRA) identified from differential metabolism-related genes was significantly associated with patient survival and may play a key role in the tumorigenesis of TETs. Our findings suggest that differential metabolic patterns in TETs are relevant to tumorigenesis and clinical outcome. Specific transcriptomic alterations in differential metabolism-related genes may serve as predictive biomarkers of survival outcomes and potential targets for the treatment of patients with TETs.

摘要

胸腺瘤和胸腺癌是恶性胸腺上皮肿瘤(TETs),如果不可切除则预后较差。然而,其肿瘤发生机制,尤其是涉及的代谢机制,研究较少。利用非靶向代谢组学分析筛选胸腺癌组织与相邻非癌组织之间的差异代谢谱。结合转录组数据,我们全面评估了TETs的代谢模式。构建代谢评分以量化单个肿瘤的代谢模式。随后对与代谢评分相关的不同临床结局和免疫格局进行了研究。在TETs之间鉴定出两种不同的代谢模式和差异代谢评分,它们富集于多种生物学途径并与临床结局相关。特别是,高代谢评分与较差的生存结局和免疫抑制状态高度相关。更重要的是,从差异代谢相关基因中鉴定出的两个预后基因(ASNS和BLVRA)的表达与患者生存显著相关,可能在TETs的肿瘤发生中起关键作用。我们的研究结果表明,TETs中的差异代谢模式与肿瘤发生和临床结局相关。差异代谢相关基因中的特定转录组改变可能作为生存结局的预测生物标志物以及TETs患者治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edfa/9228216/bd5accb25725/metabolites-12-00567-g001.jpg

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