Overexpression of NEK2 is correlated with poor prognosis in human clear cell renal cell carcinoma

Wang, Chenfeng; Huang, Yan; Ma, Xin; Wang, Qianqian

doi:10.1177/20587384211065893

Cited by 12 publications

(12 citation statements)

References 17 publications

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“…For example, Zhang and his colleague have discovered several interested genes and demonstrated their potential as target for ccRCC. NEK2, NIMA-related kinase 2, was found to be overexpressed in ccRCC and high expression of NEK2 was associated with a poor prognosis [ 56 ]. CD146 was identified to be elevated in ccRCC tissues, and high CD146 expression was associated with poor prognosis in patients with ccRCC [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of IL20RB as a Novel Prognostic and Therapeutic Biomarker in Clear Cell Renal Cell Carcinoma

et al. 2022

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Background. Clear cell renal cell carcinoma (ccRCC) is a type of life-threatening malignant tumor of the urinary system. IL20RB, interleukin 20 receptor subunit beta, is a cytokine receptor subunit coding gene and was initially found to play a vital role in human cancers, while its role in ccRCC still remains unclear. Methods. In this work, we explored the prognostic value and therapeutic potential of IL20RB in ccRCC mainly by online tools. Firstly, we used UALCAN and GEPIA to explore the expression profile and prognostic value of IL20RB in various cancers; the expression profile in tumor cell lines was also analysed with CCLE and Expression Atlas. Then, we decided to focus on ccRCC for further analysis; we further demonstrated the significant correlation between expression and clinical features by GEPIA and UALCAN. In order to reveal the potential intrinsic mechanism responsible for the upregulation of IL20RB in ccRCC, we made genetic alternation analysis and methylation analysis. cBioPortal was used for genetic alternation analysis. UALCAN, MethSurv, and Xena were used for methylation analysis. To learn details of how IL20RB might function in ccRCC, we further conducted functional analysis and immune infiltration analysis. STRING and GSEA were used to do functional analysis. TIMER was used for immune infiltration analysis; KM plotter was used for survival analysis. Results. Results show that IL20RB is upregulated in ccRCC, and low methylation may be responsible for its upregulation. Both high expression and low methylation of IL20RB predict worse survival, and both have a strong positive correlation with clinical characteristics. In addition, results indicate that there exists a crosstalk between IL20RB and neutrophils. Furthermore, the immune microenvironment could influence the prognosis predicting ability of IL20RB. Conclusions. In conclusion, IL20RB plays an important role in ccRCC and is identified as a novel prognostic and potential therapeutic biomarker in ccRCC.

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Section: Discussionmentioning

confidence: 99%

Identification of IL20RB as a Novel Prognostic and Therapeutic Biomarker in Clear Cell Renal Cell Carcinoma

et al. 2022

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“…An increasing number of studies show that NEK2 expression is increased in tumor tissues, and NEK2 upregulation is closely associated with multiple types of tumor progression, drug resistance, and poor prognosis [15][16][17]. Meanwhile, a previous study demonstrated that deregulation of NEK2 protein is associated with poor prognosis in human ccRCC [18], but to date, there have been no reports on the regulatory mechanism of NEK2 protein on ccRCC.…”

Section: Introductionmentioning

confidence: 99%

NEK2 Serves as a Novel Biomarker and Enhances the Tumorigenicity of Clear-CellRenal-Cell Carcinoma by Activating WNT/β-Catenin Pathway

Zhou

Lai

Cheng

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Currently, cumulative evidence has shown that loss of NEK2 function suppresses tumor growth. However, complete studies on the regulatory role of NEK2 in clear-cellrenal-cell carcinoma (ccRCC) are rarely reported. Methods. The GEPIA database was used for information mining to analyze the gene expression differences between ccRCC tumor and normal tissues. At the same time, we analyzed the protein expression of NEK2 in clinical ccRCC samples and ccRCC cell lines. We detected the effect of NEK2 on the biological behavior of ccRCC at the cell level and further verified the biological effect of NEK2 on ccRCC cells in vivo by nude mouse tumorigenesis experiment. The expression of WNT/β-cateninpathway-related proteins and downstream proteins related to cell function were detected by Western blotting. Results. Using the GEPIA database, we observed that NEK2 expression level in ccRCC tissues was significantly higher than that in normal kidney tissues and was also related to tumor grade. The survival time of patients with ccRCC with high NEK2 expression was shorter than that of patients with low NEK2 expression. Compared with adjacent carcinoma and normal renal tubular epithelial cells, NEK2 levels were highly expressed in ccRCC tissues and ccRCC cell lines. NEK2 interference restrained ccRCC cell growth, migration, and invasion. NEK2 regulated the malignant behavior of ccRCC cells through the WNT/β-catenin pathway. Nude mouse tumorigenesis assay results showed that the transplanted tumors from NEK2 silenced mice grew more slowly and were smaller in size than those from control mice. Conclusions. NEK2 elevation may be associated with poor prognosis in ccRCC, and NEK2 enhances ccRCC cell proliferation, migration, and invasion ability by activating the WNT/β-catenin signaling pathway.

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“…Many studies have shown that the development of ccRCC is accompanied by changes in gene expression [22][23][24][25][26]. For example, Wang et al [22] discovered that the expression of NEK2 was signi cantly upregulated in ccRCC tissues, which was associated with poor prognosis of patients. Feng et al [23] reported that overexpression of PFKFB4 mediated sunitinib resistance in ccRCC patients by promoting the pentose phosphate pathway.…”

Section: Discussionmentioning

confidence: 99%

Immune-related basement membrane genes predict the immunotherapy and prognosis of ccRCC patients

Hou

Zhu

Wang

et al. 2023

Preprint

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Background Basement membrane (BM) genes are an important factor in the process of clear cell renal cell carcinoma (ccRCC). Thus, identifying BM genes with prognostic values in ccRCC is critical. Methods The samples from TCGA were separated randomly into 2 cohorts, the training cohort, and the validation cohort. Univariate and multivariate Cox regression analyses were applied to identify prognostic BM genes. Then, nomogram was applied to predict prognosis at different clinicopathological stages and risk scores. GO and KEGG analyses were applied to identify the differentially expressed genes. Moreover, CIBERSORT and ESTIMATE scores were calculated between the high- and low-risk cohort. Results A prognostic risk model of four BM genes, including ADAMTS14, COL7A1, HSPG2, and TIMP3, was constructed. There were also significant differences in survival time between the high- and low-risk cohort for the validation cohort and the entire cohort. The risk model was validated as a new independent prognostic factor for ccRCC by univariate and multivariate Cox regression together with clinicopathological characteristics. The model can also analyze the possibility of immune escape and response to immunotherapy in ccRCC patients. In addition, the results of a pan-cancer analysis showed that these four model genes were associated with immune-related genes in a variety of cancers. Conclusion The signature of four BM genes had a significant prognostic value for ccRCC. They may be promising targets for therapy, especially immune therapy.

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Overexpression of NEK2 is correlated with poor prognosis in human clear cell renal cell carcinoma

Cited by 12 publications

References 17 publications

Identification of IL20RB as a Novel Prognostic and Therapeutic Biomarker in Clear Cell Renal Cell Carcinoma

Identification of IL20RB as a Novel Prognostic and Therapeutic Biomarker in Clear Cell Renal Cell Carcinoma

NEK2 Serves as a Novel Biomarker and Enhances the Tumorigenicity of Clear-CellRenal-Cell Carcinoma by Activating WNT/β-Catenin Pathway

Immune-related basement membrane genes predict the immunotherapy and prognosis of ccRCC patients

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