Comparative Assessment of the WNT/β-Catenin Pathway, CacyBP/SIP, and the Immunoproteasome Subunit LMP7 in Various Histological Types of Renal Cell Carcinoma

Piotrowska, Żaneta; Niezgoda, Michał; Młynarczyk, Grzegorz; Acewicz, Magdalena

doi:10.3389/fonc.2020.566637

Cited by 14 publications

(14 citation statements)

References 33 publications

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“…Aberrant DNA methylation changes on promoters, enhancers, and gene bodies contribute to alteration of gene expression and consequently affect signaling, regulatory, and metabolic pathways. Renal carcinoma has been associated with MET ( 46 ), Hippo ( 47 ), Wnt ( 48 ), MAPK ( 49 ), NRF2 (nuclear erythroid 2-related factor 2)-ARE (antioxident response element), phosphatidylinositol 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) ( 50 ), metabolic, angiogenic, and immune checkpoint–associated pathways ( 51 ). GO and pathway enrichment analysis of the MethylBoostER features mapped to genes show a strong association with genes, processes, and pathways involved in carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Accurate detection of benign and malignant renal tumor subtypes with MethylBoostER: An epigenetic marker–driven learning framework

et al. 2022

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Current gold standard diagnostic strategies are unable to accurately differentiate malignant from benign small renal masses preoperatively; consequently, 20% of patients undergo unnecessary surgery. Devising a more confident presurgical diagnosis is key to improving treatment decision-making. We therefore developed MethylBoostER, a machine learning model leveraging DNA methylation data from 1228 tissue samples, to classify pathological subtypes of renal tumors (benign oncocytoma, clear cell, papillary, and chromophobe RCC) and normal kidney. The prediction accuracy in the testing set was 0.960, with class-wise ROC AUCs >0.988 for all classes. External validation was performed on >500 samples from four independent datasets, achieving AUCs >0.89 for all classes and average accuracies of 0.824, 0.703, 0.875, and 0.894 for the four datasets. Furthermore, consistent classification of multiregion samples ( N = 185) from the same patient demonstrates that methylation heterogeneity does not limit model applicability. Following further clinical studies, MethylBoostER could facilitate a more confident presurgical diagnosis to guide treatment decision-making in the future.

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Section: Discussionmentioning

confidence: 99%

Accurate detection of benign and malignant renal tumor subtypes with MethylBoostER: An epigenetic marker–driven learning framework

et al. 2022

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“…Numerous studies have shown that various classic signaling pathways, including VHL/HIF1α ( 38 ), PI3K/Akt/mTOR ( 39 ), HGF/met ( 40 ), MAPK ( 41 ) and Wnt/β- Catenin ( 42 ), are implicated in the promotion of ccRCC. ACSL3 expression has been discovered to be positively linked with tumor suppressor genes such as p53, Pten, and VHL.…”

Section: Discussionmentioning

confidence: 99%

ACSL3 is a potential prognostic biomarker for immune infiltration in clear cell renal cell carcinoma

Zhang

Huang

et al. 2022

Front. Surg.

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ObjectiveLong-chain acyl-coenzyme A synthases (ACSLs) catalyze the activation of fatty acid and are often dysregulated in malignancies. The purpose of this research was to figure out the ACSL3's prognostic value and mechanism in clear cell renal cell carcinoma (ccRCC).MethodsThe expression of ACSL3 in ccRCC was investigated in this work using data from the GEO, TCGA, Oncomine and HPA databases. The expression differences of ACSL3 in the cell lines were further detected by qPCR and Western blot. GEPIA, MethSurv, cBioPortal, and the TIMER were used to perform survival and correlation analysis on ACSL3. GO and KEGG analyses were carried out in R using clusterProfiler and GOplot. Protein-protein interactions (PPI) are constructed from Strings website, and the results were visualized in Cytoscape software.ResultsThe expression level of ACSL3 was significantly reduced in ccRCC tissues, and its mRNA and protein expression were also significantly lower in both renal cancer cell lines. ACSL3 is significantly related to clinical stage, OS, DFS, DNA methylation, and immune-cell infiltration.ConclusionOur findings demonstrated that data mining was capable of eliciting information on ACSL3 levels and its role in genetic regulatory pathways in ccRCC.

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“…Many Wnt members were identified as biomarkers for RCC, and some of them were verified as participants in RCC development [ 49 – 52 ]. Piotrowska et al compared the activation of Wnt/β-catenin pathway among ccRCC, papillary RCC and chromophobe RCC via immunohistochemistry, finding that the Wnt pathway pronouncedly activated in ccRCC [ 53 ]. A classical mechanism of the Wnt pathway is to decrease the amount of phosphorylated GSK3β and cytoplasmic β-catenin as well as upregulate many transcription factors that could upregulate oncogene MYC and CCND1 [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Zhang

et al. 2021

J Transl Med

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Clear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of the kidney. New and reliable biomarkers are in urgent need for ccRCC diagnosis and prognosis. The CENP family is overexpressed in many types of cancers, but its functions in ccRCC have not been fully clarified. In this paper, we found that several CENP family members were highly expressed in ccRCC tissues. Also, CENPA expression level was related to clinicopathological grade and prognosis by weighted gene co-expression network analysis (WGCNA). CENPA served as a representative CENP family member as a ccRCC biomarker. Further in vitro experiments verified that overexpression of CENPA promoted ccRCC proliferation and metastasis by accelerating the cell cycle and activating the Wnt/β-catenin signaling pathway. The elevated β-catenin led by CENPA overexpression translocated to nucleus for downstream effect. Functional recovery experiment confirmed that Wnt/β-catenin pathway was essential for ccRCC progression and metastasis. Developing selective drugs targeting CENPA may be a promising direction for cancer treatment.

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Comparative Assessment of the WNT/β-Catenin Pathway, CacyBP/SIP, and the Immunoproteasome Subunit LMP7 in Various Histological Types of Renal Cell Carcinoma

Cited by 14 publications

References 33 publications

Accurate detection of benign and malignant renal tumor subtypes with MethylBoostER: An epigenetic marker–driven learning framework

Accurate detection of benign and malignant renal tumor subtypes with MethylBoostER: An epigenetic marker–driven learning framework

ACSL3 is a potential prognostic biomarker for immune infiltration in clear cell renal cell carcinoma

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

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