DLK2 Acts as a Potential Prognostic Biomarker for Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis
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 ccR...
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MDPI AG
2022-04-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/4/629 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Man-Gang Lee |
| collection | DOAJ |
| description | 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<sup>+</sup> 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. |
| first_indexed | 2024-03-09T10:36:41Z |
| format | Article |
| id | doaj.art-cb7ca30733eb42139eaaf4bb2eaa1258 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T10:36:41Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-cb7ca30733eb42139eaaf4bb2eaa12582023-12-01T20:57:02ZengMDPI AGGenes2073-44252022-04-0113462910.3390/genes13040629DLK2 Acts as a Potential Prognostic Biomarker for Clear Cell Renal Cell Carcinoma Based on Bioinformatics AnalysisMan-Gang Lee0Yung-Kuo Lee1Shih-Chung Huang2Chen-Lin Chang3Chou-Yuan Ko4Wen-Chin Lee5Tung-Yuan Chen6Shiow-Jyu Tzou7Cheng-Yi Huang8Ming-Hong Tai9Yu-Wei Lin10Mei-Lang Kung11Ming-Chao Tsai12Yung-Lung Chen13Yi-Chen Chang14Zhi-Hong Wen15Chao-Cheng Huang16Tian-Huei Chu17Department of Surgery, Division of Urology, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, TaiwanMedical Laboratory, Medical Education and Research Center, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, TaiwanDepartment of Internal Medicine, Division of Cardiology, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, TaiwanInstitute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, TaiwanInstitute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, TaiwanDepartment of Internal Medicine, Division of Nephrology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Surgery, Division of Colorectal Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, TaiwanInstitute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, TaiwanInstitute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 80424, TaiwanInstitute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 80424, TaiwanDepartment of Radiation Oncology, Kaohsiung Veterans General Hospital, Kaohsiung 813414, TaiwanDepartment of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813414, TaiwanDepartment of Internal Medicine, Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanSection of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, TaiwanDoctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 80424, TaiwanDepartment of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 80424, TaiwanDepartment of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanMedical Laboratory, Medical Education and Research Center, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, TaiwanClear 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<sup>+</sup> 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.https://www.mdpi.com/2073-4425/13/4/629clear cell renal cell carcinomadelta-like 2 homologueprognosisbiomarker |
| spellingShingle | 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 DLK2 Acts as a Potential Prognostic Biomarker for Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis Genes clear cell renal cell carcinoma delta-like 2 homologue prognosis biomarker |
| title | DLK2 Acts as a Potential Prognostic Biomarker for Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis |
| title_full | DLK2 Acts as a Potential Prognostic Biomarker for Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis |
| title_fullStr | DLK2 Acts as a Potential Prognostic Biomarker for Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis |
| title_full_unstemmed | DLK2 Acts as a Potential Prognostic Biomarker for Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis |
| title_short | DLK2 Acts as a Potential Prognostic Biomarker for Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis |
| title_sort | dlk2 acts as a potential prognostic biomarker for clear cell renal cell carcinoma based on bioinformatics analysis |
| topic | clear cell renal cell carcinoma delta-like 2 homologue prognosis biomarker |
| url | https://www.mdpi.com/2073-4425/13/4/629 |
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