BUB1B Overexpression Is an Independent Prognostic Marker and Associated with CD44, p53, and PD-L1 in Renal Cell Carcinoma

Oncology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Yohei Sekino ◽  
Xiangrui Han ◽  
Go Kobayashi ◽  
Takashi Babasaki ◽  
Shunsuke Miyamoto ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Growth ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Renal Cell ◽  
Spindle Assembly Checkpoint ◽  
Mitotic Checkpoint ◽  
Stem Cell Markers ◽  
Poor Overall Survival ◽  
Cancer Stem Cell Markers

<b><i>Introduction:</i></b> BUB1 mitotic checkpoint serine/threonine kinase B encoded by <i>BUB1B</i> gene is a member of the spindle assembly checkpoint family. Several reports have demonstrated that overexpression of BUB1B is associated with cancer progression and prognosis. <b><i>Objective:</i></b> This study aims to clarify the expression and function of BUB1B in renal cell carcinoma (RCC). <b><i>Methods:</i></b> The expression of BUB1B was determined using immunohistochemistry and bioinformatics analysis in RCC. The effects of BUB1B knockdown on cell growth and invasion were evaluated. We analyzed the interaction between BUB1B, cancer stem cell markers, p53, and PD-L1 in RCC. <b><i>Results:</i></b> In 121 cases of RCC, immunohistochemistry showed that 30 (25%) of the RCC cases were positive for BUB1B. High BUB1B expression was significantly correlated with high nuclear grade, T stage, and M stage. A Kaplan-Meier analysis showed that the high expression of BUB1B was associated with poor overall survival after nephrectomy. High BUB1B expression was associated with CD44, p53, and PD-L1 in RCC. Knockdown of BUB1B suppressed cell growth and invasion in RCC cell lines. Knockdown of BUB1B also suppressed the expression of CD44 and increased the expression of phospho-p53 (Ser15). In silico analysis showed that BUB1B was associated with inflamed CD8+, exhausted T-cell signature, IFN-γ signature, and the response to nivolumab. <b><i>Conclusion:</i></b> These results suggest that BUB1B plays an oncogenic role and may be a promising predictive biomarker for survival in RCC.

scholarly journals Cancer stem cell markers predict a poor prognosis in renal cell carcinoma: a meta-analysis

Oncotarget ◽  
2016 ◽  
Vol 7 (40) ◽  
pp. 65862-65875 ◽  
Author(s):  
Bo Cheng ◽  
Guosheng Yang ◽  
Rui Jiang ◽  
Yong Cheng ◽  
Haifan Yang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Meta Analysis ◽  
Stem Cell Markers ◽  
Cell Markers ◽  
Cancer Stem Cell Markers

scholarly journals DDX3X is Epigenetically Repressed in Renal Cell Carcinoma and Serves as a Prognostic Indicator and Therapeutic Target in Cancer Progression

2020 ◽  
Vol 21 (8) ◽  
pp. 2881
Author(s):  
Tsung-Chieh Lin
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Renal Cell ◽  
Biological Effects ◽  
The Cancer Genome Atlas ◽  
Prognostic Indicators ◽  
Rna Helicases ◽  
Poor Overall Survival ◽  
Expression Levels

DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked (DDX3X) is a member of the DEAD-box family of RNA helicases whose function has been revealed to be involved in RNA metabolism. Recent studies further indicate the abnormal expression in pan-cancers and the relevant biological effects on modulating cancer progression. However, DDX3X’s role in renal cell carcinoma (RCC) progression remains largely unknown. In this study, a medical informatics-based analysis using The Cancer Genome Atlas (TCGA) dataset was performed to evaluate clinical prognoses related to DDX3X. The results suggest that DDX3X is epigenetically repressed in tumor tissue and that lower DDX3X is correlated with the poor overall survival of RCC patients and high tumor size, lymph node metastasis, and distant metastasis (TNM staging system). Furthermore, knowledge-based transcriptomic analysis by Ingenuity Pathway Analysis (IPA) revealed that the SPINK1-metallothionein pathway is a top 1-repressed canonical signaling pathway by DDX3X. Furthermore, SPINK1 and the metallothionein gene family all serve as poor prognostic indicators, and the expression levels of those genes are inversely correlated with DDX3X in RCC. Furthermore, digoxin was identified via Connectivity Map analysis (L1000) for its capability to reverse gene signatures in patients with low DDX3X. Importantly, cancer cell proliferation and migration were decreased upon digoxin treatment in RCC cells. The results of this study indicate the significance of the DDX3Xlow/SPINK1high/metallothioneinhigh axis for predicting poor survival outcome in RCC patients and suggest digoxin as a precise and personalized compound for curing those patients with low DDX3X expression levels.

scholarly journals SNU-333 Cells as an Appropriate Cell Line for the Orthotopic Renal Cell Carcinoma Model

2021 ◽  
Vol 20 ◽  
pp. 153303382110384
Author(s):  
Inyoub Chang ◽  
Takbum Ohn ◽  
Daeun Moon ◽  
Young Hee Maeng ◽  
Bo Gun Jang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Renal Cell ◽  
Epithelial Mesenchymal Transition ◽  
Stem Cell Markers ◽  
Mesenchymal Transition ◽  
Cancer Stem Cell Markers

Objective: To investigate a feasible candidate for an appropriate cell line for the orthotopic renal cell carcinoma (RCC) model. Methods: Normal human proximal tubule cells (HK-2) and RCC cells were used for MTT assay, Western blotting, sphere-forming assay, and orthotopic injection of BALB/c-nude mice. Immunohistochemistry was adopted in tissue arrays and orthotopic tumors. Results: Primary RCC cells showed resistance to a GPX4 inhibitor compared to HK-2 and to metastatic RCC cells, Caki-1. Caki-2 and SNU-333 cells showed resistance to ferroptosis via increased GPX4 and FTH1, respectively. RCC cells showed increased αSMA, in which Caki-2 and SNU-333 cells exhibited different epithelial–mesenchymal transition and cancer stem cell markers. Caki-1 and SNU-333 cells formed spheres in vitro and orthotopic tumor masses in vivo. The injected SNU-333 tumor only showed high intensities of CD10 and PAX8, markers of renal origin. Conclusion: SNU-333 cell line exhibited resistance via iron metabolism and stemness, and had tumor-initiating capacities in vitro and in vivo. These results suggest that among the cells tested, SNU-333 cells were the most promising for the establishment of an orthotopic RCC model for further researches.

scholarly journals Metabolomic Analysis to Elucidate Mechanisms of Sunitinib Resistance in Renal Cell Carcinoma

Metabolites ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 1
Author(s):  
Tomonori Sato ◽  
Yoshihide Kawasaki ◽  
Masamitsu Maekawa ◽  
Shinya Takasaki ◽  
Kento Morozumi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Energy Metabolism ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Progression ◽  
Renal Cell ◽  
Treatment Resistance ◽  
Tca Cycle ◽  
Glutamine Uptake

Metabolomics analysis possibly identifies new therapeutic targets in treatment resistance by measuring changes in metabolites accompanying cancer progression. We previously conducted a global metabolomics (G-Met) study of renal cell carcinoma (RCC) and identified metabolites that may be involved in sunitinib resistance in RCC. Here, we aimed to elucidate possible mechanisms of sunitinib resistance in RCC through intracellular metabolites. We established sunitinib-resistant and control RCC cell lines from tumor tissues of RCC cell (786-O)-injected mice. We also quantified characteristic metabolites identified in our G-Met study to compare intracellular metabolism between the two cell lines using liquid chromatography-mass spectrometry. The established sunitinib-resistant RCC cell line demonstrated significantly desuppressed protein kinase B (Akt) and mesenchymal-to-epithelial transition (MET) phosphorylation compared with the control RCC cell line under sunitinib exposure. Among identified metabolites, glutamine, glutamic acid, and α-KG (involved in glutamine uptake into the tricarboxylic acid (TCA) cycle for energy metabolism); fructose 6-phosphate, D-sedoheptulose 7-phosphate, and glucose 1-phosphate (involved in increased glycolysis and its intermediate metabolites); and glutathione and myoinositol (antioxidant effects) were significantly increased in the sunitinib-resistant RCC cell line. Particularly, glutamine transporter (SLC1A5) expression was significantly increased in sunitinib-resistant RCC cells compared with control cells. In this study, we demonstrated energy metabolism with glutamine uptake and glycolysis upregulation, as well as antioxidant activity, was also associated with sunitinib resistance in RCC cells.

CD151 expression can predict cancer progression in clear cell renal cell carcinoma

2011 ◽  
Vol 58 (2) ◽  
pp. 191-197 ◽  
Author(s):  
Seong H Yoo ◽  
Kyoungbun Lee ◽  
Ji Y Chae ◽  
Kyung C Moon
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

scholarly journals Downregulation of miR-193a-3p inhibits cell growth and migration in renal cell carcinoma by targeting PTEN

Tumor Biology ◽  
2017 ◽  
Vol 39 (6) ◽  
pp. 101042831771195 ◽  
Author(s):  
Lingqi Liu ◽  
Yanqin Li ◽  
Shuchao Liu ◽  
Qixin Duan ◽  
Liang Chen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Growth ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Growth And Migration ◽  
And Migration

scholarly journals B7-H4 expression in renal cell carcinoma and tumor vasculature: Associations with cancer progression and survival

2006 ◽  
Vol 103 (27) ◽  
pp. 10391-10396 ◽  
Author(s):  
A. E. Krambeck ◽  
R. H. Thompson ◽  
H. Dong ◽  
C. M. Lohse ◽  
E. S. Park ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Renal Cell ◽  
Tumor Vasculature

scholarly journals Identification Of Gene Signature For Renal Cell Carcinoma-Associated Fibroblasts Mediating Cancer Progression And Affecting Prognosis

2020 ◽  
Author(s):  
Bitian Liu ◽  
Xiaonan Chen ◽  
Yunhong Zhan ◽  
Bin Wu ◽  
Shen Pan
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Single Cell ◽  
Clinical Significance ◽  
Cell Lines ◽  
Cancer Progression ◽  
Renal Cell ◽  
Gene Signature ◽  
Pathological Grade ◽  
Single Cell Sequencing

Abstract Background: Cancer-associated fibroblasts (CAFs) are most abundant in stroma and are critically involved in cancer progression. However, the specific signature of CAFs and related clinicopathological parameters in renal cell carcinoma (RCC) remain unclear. Methods: In this work, methods using recognized gene signatures were employed to roughly assess the infiltration level of the stroma and CAFs in RCC based on the data in The Cancer Genome Atlas. Weighted gene co-expression network analysis (WGCNA) was used to cluster transcriptomes and correlate with CAFs to identify specific markers. A comparison of fibroblast versus urothelial carcinoma cell lines and correlation with previously reported CAF markers were performed to demonstrate the specific expressed of the gene signature. The gene signature was used to compare fibroblast infiltration of each sample through single sample gene set enrichment analysis, and the clinical significance of fibroblasts was analyzed via Cox risk assessment and the chi-square test. Finally, we used validation data to verify the clinical significance of the fibroblast gene signature in RCC. Results: Roughly calculated tumor matrix and CAF levels were significantly higher in kidney cancer than in normal tissues. More than 85% of fibroblast-specific markers identified by WGCNA were consistent with markers obtained via single-cell sequencing. These markers were more highly expressed in fibroblast cell lines and were significantly correlated with canonical CAFs makers. Data validation also showed that CAFs were significant correlation with survival and pathological grade. Conclusions: In summary, our findings indicate that the gene signature potentially serves as a biomarker of CAFs in RCC and that infiltration of fibroblasts in RCC is an independent prognostic factor associated with pathological grade and stage of tumor. The ability to recognize specific CAF markers using WGCNA is comparable to single-cell sequencing.

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