CENPA promotes clear cell renal cell carcinoma progression and metastasis via Wnt/β-catenin signaling pathway

Wang, Qi; Xu, Jiaju; Zhang, Xiong; Xu, Tianbo; Liu, Jingchong; Liu, Yuenan; Chen, Jiaping; Shi, Jian; Shou, Yanhong; Yue, Changjie; Liu, Di; Liang, Huageng; Yang, Hongmei; Yang, Xiong; Zhang, Xiaoping

doi:10.1186/s12967-021-03087-8

Cited by 48 publications

(31 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CENP-A overexpression plays a pivotal role in chromosomal instability and pathogenesis of malignancies through chromosome segregation defects ( Shrestha et al, 2017 ), a mechanism involved CENP-A in cancers ( Sun et al, 2016 ; Sharma et al, 2019 ). In addition, elevated CENP-A levels promote the proliferation of cancer cells in hepatoma ( Li et al, 2011 ), prostate ( Saha et al, 2020 ) and renal cell carcinoma ( Wang et al, 2021a ). The observations support an association of CENP-A function with cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…Besides a role in cell proliferation following malignant transformation, in the cellular context of defective p53 ( Filipescu et al, 2017 ; Jeffery et al, 2021 ), CENP-A overexpression stimulates epithelial-mesenchymal transition, a major contributing factor in the metastasis of cancer cells ( Jeffery et al, 2021 ). CENP-A expression was positively associated with cancer metastasis in gastric ( Xu et al, 2020 ) and renal ( Wang et al, 2021a ) cancers. Taking the evidence together, we believe that CENP-A overexpression is related to malignant transformation, tumor invasiveness and metastasis in specific cancer contexts.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

CENP-A is a potential prognostic biomarker and correlated with immune infiltration levels in glioma patients

et al. 2022

View full text Add to dashboard Cite

Background: Centromeric protein A (CENP-A), an essential protein involved in chromosomal segregation during cell division, is associated with several cancer types. However, its role in gliomas remains unclear. This study examined the clinical and prognostic significance of CENP-A in gliomas.Methods: Data of patients with glioma were collected from the Cancer Genome Atlas. Logistic regression, the Kruskal–Wallis test, and the Wilcoxon signed-rank test were performed to assess the relationship between CENP-A expression and clinicopathological parameters. The Cox regression model and Kaplan–Meier curve were used to analyze the association between CENP-A and survival outcomes. A prognostic nomogram was constructed based on Cox multivariate analysis. Gene set enrichment analysis (GSEA) was conducted to identify key CENP-A-related pathways and biological processes.Results:CENP-A was upregulated in glioma samples. Increased CENP-A levels were significantly associated with the world health organization (WHO) grade [Odds ratio (OR) = 49.88 (23.52–129.06) for grade 4 vs. grades 2 and 3], primary therapy outcome [OR = 2.44 (1.64–3.68) for progressive disease (PD) and stable disease (SD) vs. partial response (PR) and complete response (CR)], isocitrate dehydrogenase (IDH) status [OR = 13.76 (9.25–20.96) for wild-type vs. mutant], 1p/19q co-deletion [OR = 5.91 (3.95–9.06) for no codeletion vs. co-deletion], and age [OR = 4.02 (2.68–6.18) for > 60 vs. ≤ 60]. Elevated CENP-A expression was correlated with shorter overall survival in both univariate [hazard ratio (HR): 5.422; 95% confidence interval (CI): 4.044–7.271; p < 0.001] and multivariate analyses (HR: 1.967; 95% CI: 1.280–3.025; p < 0.002). GSEA showed enrichment of numerous cell cycle-and tumor-related pathways in the CENP-A high expression phenotype. The calibration plot and C-index indicated the favorable performance of our nomogram for prognostic prediction in patients with glioma.Conclusion: We propose a role for CENP-A in glioma progression and its potential as a biomarker for glioma diagnosis and prognosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CENP-A is a potential prognostic biomarker and correlated with immune infiltration levels in glioma patients

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Centromere protein (CENP) has been identi ed as an autoantibody target in human disease and autoantibodies against CENPA, CENPB and CENPC have been considered relatively speci c biomarkers for calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome [23]. In recent years, evidence for the CENP family in human cancers has been presented, including lung, breast, prostate and kidney cancers [11,[24][25][26]. CENPM, a component of the CENPA-nucleosome associated complex, has also been reported to be associated with liver and pancreatic cancers [8,9].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of CENPM is associated with poor clinical outcome and suppression of immune profile in clear cell renal cell carcinoma

Zhang

Liu

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: The response of advanced clear cell renal cell carcinoma (ccRCC) to immunotherapy is still not durable, suggesting that the immune landscape of ccRCC still needs to be refined, especially as some molecules that have synergistic effects with immune checkpoint genes need to be explored.Methods: The expression levels of CENPM and its relationship with clinicopathological features were explored using the ccRCC dataset from TCGA and GEO databases. Quantitative polymerase chain reaction (qPCR) analysis was performed to validate the expression of CENPM in renal cancer cell lines. ROC curves, Kaplan-Meier analysis, COX regression analysis and Nomogram construction were used to systematically evaluate the diagnostic and prognostic potential of CENPM in ccRCC. Besides, single gene correlation analysis, protein–protein interaction (PPI) network, genetic ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to predict the biological behaviour of CENPM and the possible signalling pathways involved. Finally, a comprehensive analysis of the crosstalk between CENPM and immune features in the tumor microenvironment was performed based on the ssGSEA algorithm, the tumor immune dysfunction and exclusion (TIDE) algorithm, the TIMER2.0 database and the TISIDB database.Results: CENPM was significantly upregulated in ccRCC tissues and renal cancer cell lines and was closely associated with poor clinicopathological features and prognosis. Pathway enrichment analysis revealed that CENPM may be involved in the regulation of the cell cycle in ccRCC and may have some crosstalk with the immune microenvironment in tumors. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. Furthermore, the TISIDB database provides evidence that not only CENPM is positively associated with immune checkpoint genes such as CTLA4, PDCD1, LAG3, TIGIT, but also chemokines and receptors (such as CCL5, CXCL13, CXCR3, CXCR5) may be responsible for the malignant phenotype of CENPM in ccRCC. Meanwhile, predictions based on the TIDE algorithm support that patients with high CENPM expression have a worse response to immunotherapy.Conclusions: The upregulation of CENPM in ccRCC predicts a poor clinical outcome, and this malignant phenotype may be associated with its exacerbation of the immunosuppressive state in the tumor microenvironment.

show abstract

“…Furthermore, SASP-mediated endothelial activation stimulates CD8 + T cell recruitment into otherwise immunologically “cold” tumors, thereby sensitizing tumors to PD-1 checkpoint blockade ( Ruscetti et al, 2020 ). CENPA has been reported to be an oncogene in various malignancies, including PDAC ( Furukawa et al, 2006 ; Zhang et al, 2020 ; Han et al, 2021 ; Wang et al, 2021 ). Wang et al (2021) revealed that CENPA overexpression promotes the proliferation and metastasis of clear cell renal cell carcinoma by activating the Wnt/β-catenin signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of senescence-associated genes in pancreatic ductal adenocarcinoma

Zhu

Chen²,

Miao³

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

Background: Cellular senescence plays a critical role in the occurrence and development, and immune modulation of cancer. This research primarily investigated the role of senescence-associated genes (SAGs) in the survival and tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC).Methods: From the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database, the gene expression profiles and clinical data of PDAC samples were downloaded. SAGs in the TCGA cohort were used to build a novel prognostic model and validated in the ICGC cohort. The relationship of signature with the immune landscape, tumor mutational burden (TMB), as well as the sensitivity of different therapies, was explored. Moreover, a nomogram was developed to predict the overall survival of PDAC patients.Results: A prognostic signature was constructed on basis of three SAGs, and patients in the low-risk score group had a longer survival time. The accuracy of the signature to distinguish different score groups was confirmed through principal component analysis (PCA) and the Receiver operator curves curve. The mRNA expression of the three signature genes was also verified in normal pancreatic and PDAC cell lines by RT-qPCR. The signature could independently predict the prognosis of PDAC patients and had broad applicability. Meanwhile, the nomogram predicted that 1- and 3-years survival rates were in good agreement with the observed overall survival rates. Low-risk patients had lower tumor mutational burden, and low-TMB patients had a better prognosis. Low- and high-risk patients exhibit distinct immune cell infiltration and immune checkpoint changes. By further analyzing the risk score, patients in the low-risk group were more responsive to immunotherapy and a variety of commonly used chemotherapeutic drugs.Conclusion: The prognostic signature can well predict the prognosis and assess the possibility of immunotherapy in personalized PDAC treatment.

show abstract

CENPA promotes clear cell renal cell carcinoma progression and metastasis via Wnt/β-catenin signaling pathway

Cited by 48 publications

References 64 publications

CENP-A is a potential prognostic biomarker and correlated with immune infiltration levels in glioma patients

CENP-A is a potential prognostic biomarker and correlated with immune infiltration levels in glioma patients

Upregulation of CENPM is associated with poor clinical outcome and suppression of immune profile in clear cell renal cell carcinoma

Integrated analysis of senescence-associated genes in pancreatic ductal adenocarcinoma

Contact Info

Product

Resources

About