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

被引:6
作者
Lee, Man-Gang [1 ,2 ]
Lee, Yung-Kuo [3 ]
Huang, Shih-Chung [4 ,5 ,6 ]
Chang, Chen-Lin [6 ,7 ]
Ko, Chou-Yuan [6 ,8 ,9 ]
Lee, Wen-Chin [10 ,11 ]
Chen, Tung-Yuan [12 ]
Tzou, Shiow-Jyu [6 ,13 ]
Huang, Cheng-Yi [14 ,15 ]
Tai, Ming-Hong [14 ,16 ]
Lin, Yu-Wei [17 ]
Kung, Mei-Lang [18 ]
Tsai, Ming-Chao [19 ]
Chen, Yung-Lung [20 ]
Chang, Yi-Chen [21 ,22 ]
Wen, Zhi-Hong [23 ]
Huang, Chao-Cheng [11 ,24 ,25 ]
Chu, Tian-Huei [3 ]
机构
[1] Kaohsiung Armed Forces Gen Hosp, Dept Surg, Div Urol, Kaohsiung 80284, Taiwan
[2] Kaohsiung Armed Forces Gen Hosp, Dept Surg, Div Urol, Zuoying Branch, Kaohsiung 81342, Taiwan
[3] Kaohsiung Armed Forces Gen Hosp, Med Educ & Res Ctr, Med Lab, Kaohsiung 80284, Taiwan
[4] Kaohsiung Armed Forces Gen Hosp, Dept Internal Med, Div Cardiol, Kaohsiung 80284, Taiwan
[5] Natl Def Med Ctr, Triserv Gen Hosp, Dept Internal Med, Div Cardiol, Taipei 11490, Taiwan
[6] Natl Sun Yat Sen Univ, Inst Med Sci & Technol, Kaohsiung 80424, Taiwan
[7] Kaohsiung Armed Forces Gen Hosp, Dept Psychiat, Kaohsiung 80284, Taiwan
[8] Kaohsiung Armed Forces Gen Hosp, Dept Internal Med, Div Gastroenterol & Hepatol, Kaohsiung 80284, Taiwan
[9] Natl Def Med Ctr, Triserv Gen Hosp, Dept Internal Med, Div Gastroenterol & Hepatol, Taipei 11490, Taiwan
[10] Kaohsiung Chang Gung Mem Hosp, Div Nephrol, Dept Internal Med, Kaohsiung 83301, Taiwan
[11] Chang Gung Univ, Coll Med, Kaohsiung 83301, Taiwan
[12] Kaohsiung Armed Forces Gen Hosp, Dept Surg, Div Colorectal Surg, Kaohsiung 80284, Taiwan
[13] Kaohsiung Armed Forces Gen Hosp, Dept Nursing, Kaohsiung 80284, Taiwan
[14] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 80424, Taiwan
[15] Kaohsiung Armed Forces Gen Hosp, Dept Pathol, Kaohsiung 80284, Taiwan
[16] Natl Sun Yat Sen Univ, Ctr Neurosci, Kaohsiung 80424, Taiwan
[17] Kaohsiung Vet Gen Hosp, Dept Radiat Oncol, Kaohsiung 813414, Taiwan
[18] Kaohsiung Vet Gen Hosp, Dept Med Educ & Res, Kaohsiung 813414, Taiwan
[19] Chang Gung Univ, Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Div Hepatogastroenterol,Coll Med, Kaohsiung 83301, Taiwan
[20] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Sect Cardiol, Kaohsiung 83301, Taiwan
[21] Natl Sun Yat Sen Univ, Doctoral Degree Program Marine Biotechnol, Kaohsiung 80424, Taiwan
[22] Acad Sinica, Kaohsiung 80424, Taiwan
[23] Natl Sun Yat Sen Univ, Asia Pacific Ocean Res Ctr, Dept Marine Biotechnol & Resources, Kaohsiung 80424, Taiwan
[24] Kaohsiung Chang Gung Mem Hosp, Dept Pathol, Kaohsiung 83301, Taiwan
[25] Kaohsiung Chang Gung Mem Hosp, Biobank & Tissue Bank, Kaohsiung 83301, Taiwan
关键词
clear cell renal cell carcinoma; delta-like; 2; homologue; prognosis; biomarker; GENES; IDENTIFICATION; INFILTRATION; EXPRESSION; PROTEINS; S6;
D O I
10.3390/genes13040629
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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-beta 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.
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页数:22
相关论文
共 81 条
[21]   Ribosomal s6 protein kinase 4: a prognostic factor for renal cell carcinoma [J].
Fan, L. ;
Li, P. ;
Yin, Z. ;
Fu, G. ;
Liao, D. J. ;
Liu, Y. ;
Zhu, J. ;
Zhang, Y. ;
Wang, L. ;
Yan, Q. ;
Guo, Y. ;
Shao, C. ;
Huang, G. ;
Wang, Z. .
BRITISH JOURNAL OF CANCER, 2013, 109 (05) :1137-1146
[22]   Upregulation of lncRNA AGAP2-AS1 is an independent predictor of poor survival in patients with clear cell renal carcinoma [J].
Gao, Lei ;
Zhao, Anning ;
Wang, Xiaolu .
ONCOLOGY LETTERS, 2020, 19 (06) :3993-4001
[23]  
Garcés C, 1999, DIFFERENTIATION, V64, P103, DOI 10.1007/s002580050265
[24]  
Garcia-Gallastegi P, 2019, HISTOCHEM CELL BIOL, V152, P47, DOI 10.1007/s00418-019-01778-4
[25]   Delta-like 1 homologue promotes tumorigenesis and epithelial-mesenchymal transition of ovarian high-grade serous carcinoma through activation of Notch signaling [J].
Huang, Chao-Cheng ;
Cheng, Shih-Hsuan ;
Wu, Chen-Hsuan ;
Li, Wen-Yuan ;
Wang, Jiang-Shiang ;
Kung, Mei-Lang ;
Chu, Tian-Huei ;
Huang, Shih-Tsung ;
Feng, Chien-Ting ;
Huang, Shih-Chung ;
Tai, Ming-Hong .
ONCOGENE, 2019, 38 (17) :3201-3215
[26]   Soluble delta-like 1 homolog (DLK1) stimulates angiogenesis through Notch1/Akt/eNOS signaling in endothelial cells [J].
Huang, Chao-Cheng ;
Kuo, Hsiao-Mei ;
Wu, Pei-Chang ;
Cheng, Shih-Hsuan ;
Chang, Tzu-Ting ;
Chang, Yi-Chen ;
Kung, Mei-Lang ;
Wu, Deng-Chyang ;
Chuang, Jiin-Haur ;
Tai, Ming-Hong .
ANGIOGENESIS, 2018, 21 (02) :299-312
[27]   Identification of Hub Genes Associated With Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis [J].
Huang, Hao ;
Zhu, Ling ;
Huang, Chao ;
Dong, Yi ;
Fan, Liangliang ;
Tao, Lijian ;
Peng, Zhangzhe ;
Xiang, Rong .
FRONTIERS IN ONCOLOGY, 2021, 11
[28]   Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice [J].
Jayasingam, Sharmilla Devi ;
Citartan, Marimuthu ;
Thang, Thean Hock ;
Zin, Anani Aila Mat ;
Ang, Kai Cheen ;
Ch'ng, Ewe Seng .
FRONTIERS IN ONCOLOGY, 2020, 9
[29]   Cancer statistics, 2007 [J].
Jemal, Ahmedin ;
Siegel, Rebecca ;
Ward, Elizabeth ;
Murray, Taylor ;
Xu, Jiaquan ;
Thun, Michael J. .
CA-A CANCER JOURNAL FOR CLINICIANS, 2007, 57 (01) :43-66
[30]   Mining TCGA database for genes of prognostic value in glioblastoma microenvironment [J].
Jia, Di ;
Li, Shenglan ;
Li, Dali ;
Xue, Haipeng ;
Yang, Dan ;
Liu, Ying .
AGING-US, 2018, 10 (04) :592-605