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

Man Gang Lee, Yung Kuo Lee, Shih Chung Huang, Chen Lin Chang, Chou Yuan Ko, Wen Chin Lee, Tung Yuan Chen, Shiow Jyu Tzou, Cheng Yi Huang, Ming Hong Tai, Yu Wei Lin, Mei Lang Kung, Ming Chao Tsai, Yung Lung Chen, Yi Chen Chang, Zhi Hong Wen, Chao Cheng Huang*, Tian Huei Chu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

3 Scopus citations


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.

Original languageEnglish
Article number629
Issue number4
StatePublished - 04 2022

Bibliographical note

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© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • biomarker
  • clear cell renal cell carcinoma
  • delta-like 2 homologue
  • prognosis


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