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DLK2 通过生物信息学分析作为透明细胞肾细胞癌的潜在预后生物标志物。

DLK2 Acts as a Potential Prognostic Biomarker for Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis.

机构信息

Department of Surgery, Division of Urology, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan.

Department of Surgery, Division of Urology, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung 81342, Taiwan.

出版信息

Genes (Basel). 2022 Apr 1;13(4):629. doi: 10.3390/genes13040629.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common RCC subtype with a high mortality. It has been reported that delta-like 1 homologue (DLK1) participates in the tumor microenvironmental remodeling of ccRCC, but the relationship between delta-like 2 homologue (DLK2, a DLK1 homologue) and ccRCC is still unclear. Thus, this study aims to investigate the role of DLK2 in the biological function and disease prognosis of ccRCC using bioinformatics analysis. The TNMplot database showed that DLK2 was upregulated in ccRCC tissues. From the UALCAN analysis, the overexpression of DLK2 was associated with advanced stage and high grade in ccRCC. Moreover, the Kaplan-Meier plotter (KM Plotter) database showed that DLK2 upregulation was associated with poor survival outcome in ccRCC. By the LinkedOmics analysis, DLK2 signaling may participated in the modulation of ccRCC extracellular matrix (ECM), cell metabolism, ribosome biogenesis, TGF-β signaling and Notch pathway. Besides, Tumor Immune Estimation Resource (TIMER) analysis showed that the macrophage and CD8 T cell infiltrations were associated with good prognosis in ccRCC patients. Finally, DLK2 overexpression was associated with the reduced macrophage recruitments and the M1-M2 polarization of macrophage in ccRCC tissues. Together, DLK2 may acts as a novel biomarker, even therapeutic target in ccRCC. However, this study lacks experimental validation, and further studies are required to support this viewpoint.

摘要

透明细胞肾细胞癌(ccRCC)是最常见的 RCC 亚型,死亡率较高。有报道称,δ样蛋白 1 同源物(DLK1)参与 ccRCC 的肿瘤微环境重塑,但 δ样蛋白 2 同源物(DLK2,DLK1 的同源物)与 ccRCC 的关系尚不清楚。因此,本研究旨在通过生物信息学分析探讨 DLK2 在 ccRCC 生物学功能和疾病预后中的作用。TNMplot 数据库显示 DLK2 在 ccRCC 组织中上调。UALCAN 分析显示,DLK2 的过表达与 ccRCC 的晚期和高级别有关。此外,Kaplan-Meier plotter(KM Plotter)数据库显示,DLK2 的上调与 ccRCC 的不良生存结局相关。通过 LinkedOmics 分析,DLK2 信号可能参与了 ccRCC 细胞外基质(ECM)、细胞代谢、核糖体生物发生、TGF-β信号和 Notch 通路的调节。此外,Tumor Immune Estimation Resource(TIMER)分析显示,巨噬细胞和 CD8+T 细胞浸润与 ccRCC 患者的良好预后相关。最后,DLK2 的过表达与 ccRCC 组织中巨噬细胞募集减少和巨噬细胞 M1-M2 极化有关。总之,DLK2 可能作为一种新的生物标志物,甚至是 ccRCC 的治疗靶点。然而,本研究缺乏实验验证,需要进一步的研究来支持这一观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b2/9030291/5431f525d65b/genes-13-00629-g001.jpg

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