Biomarkers of Bladder Cancer: Cell-Free DNA, Epigenetic Modifications and Non-Coding RNAs

Harsanyi, Stefan; Nováková, Zuzana; Bevizova, Katarina; Danišovič, Ľuboš; Žiaran, Stanislav

doi:10.3390/ijms232113206

Cited by 14 publications

(11 citation statements)

References 139 publications

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“…BLCA progression is considered a long-term, multi-step process. Besides genetics, studies have also indicated that epigenetic regulation participates in BLCA progression ( 32 , 33 ). CBX family proteins are important components of epigenetic regulatory complexes and are involved in chromatin modification, and the pathogenesis and progression of a number of tumors ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis reveals the value of the expression of chromobox family members for bladder urothelial carcinoma prognosis

et al. 2023

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Bladder urothelial carcinoma (BLCA) accounts for 95% of all cases of bladder cancer worldwide, with a high incidence and poor prognosis. Chromobox (CBX) proteins play a key role in numerous malignant tumors; however, the role of CBX in BLCA remains unknown. Herein, the present study found that, compared with in normal bladder tissues, the expression levels of CBX1, CBX2, CBX3, CBX4 and CBX8 were markedly increased in BLCA tissues, as determined by Tumor Immune Estimation Resource, UALCAN and ONCOMINE analyses, whereas CBX6 and CBX7 were decreased in BLCA tissues. Furthermore, evident hypomethylation in the promoters of CBX1, and CBX2, as well as significant hypermethylation in the promoters of CBX5, CBX6 and CBX7, was detected in BLCA tissues compared with in normal bladder tissues. The expression of CBX1, CBX2 and CBX7 was involved in the prognosis of patients with BLCA. Low CBX7 expression was strongly associated with poorer overall survival in patients with BLCA, whereas high CBX1 and CBX2 expression was associated with poorer progression-free survival. Besides, significant associations were determined between the expression of CBXs and immune cell infiltration, including dendritic cells, neutrophils, macrophages, CD4 + T cells, CD8 + T cells and B cells. Overall, the current results may provide a rationale for developing new targets and prognostic markers for BLCA therapy.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis reveals the value of the expression of chromobox family members for bladder urothelial carcinoma prognosis

et al. 2023

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“…Non-coding RNAs, such as microRNA (miRNA) and long non-coding RNA (lncRNA), play pivotal roles in gene regulation and biological processes in both health and disease, including cancer initiation and progression. Therefore, they are recognized as potential diagnostic and prognostic markers as well as therapeutic targets for cancers, including bladder UC [ 44 ]. Increasing evidence has indicated that ferroptosis is associated with cancer initiation, progression, and suppression [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Evodiamine Exhibits Anti-Bladder Cancer Activity by Suppression of Glutathione Peroxidase 4 and Induction of Ferroptosis

Shan

et al. 2023

IJMS

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Evodiamine (EVO) exhibits anti-cancer activity through the inhibition of cell proliferation; however, little is known about its underlying mechanism. To determine whether ferroptosis is involved in the therapeutic effects of EVO, we investigated critical factors, such as lipid peroxidation levels and glutathione peroxidase 4 (GPX4) expression, under EVO treatment. Our results showed that EVO inhibited the cell proliferation of poorly differentiated, high-grade bladder cancer TCCSUP cells in a dose- and time-dependent manner. Lipid peroxides were detected by fluorescence microscopy after cancer cell exposure to EVO. GPX4, which catalyzes the conversion of lipid peroxides to prevent cells from undergoing ferroptosis, was decreased dose-dependently by EVO treatment. Given the features of iron dependency and lipid-peroxidation-driven death in ferroptosis, the iron chelator deferoxamine (DFO) was used to suppress EVO-induced ferroptosis. The lipid peroxide level significantly decreased when cells were treated with DFO prior to EVO treatment. DFO also attenuated EVO-induced cell death. Co-treatment with a pan-caspase inhibitor or necroptosis inhibitor with EVO did not alleviate cancer cell death. These results indicate that EVO induces ferroptosis rather than apoptosis or necroptosis. Furthermore, EVO suppressed the migratory ability, decreased the expression of mesenchymal markers, and increased epithelial marker expression, determined by a transwell migration assay and Western blotting. The TCCSUP bladder tumor xenograft tumor model confirmed the effects of EVO on the inhibition of tumor growth and EMT. In conclusion, EVO is a novel inducer for activating the ferroptosis of bladder cancer cells and may be a potential therapeutic agent for bladder cancer.

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“…Several non-invasive urine-based tests have been developed to complement invasive cystoscopy for BC diagnosis utilizing materials in the urine (e.g., urine cytology, BTA, UroVysion, uCyt+, and NMP22) [4][5][6][7]. However, these tests have poor accuracy in detecting BC, with sensitivities between 56% and 83% and specificities between 64% and 88%.…”

Section: Introductionmentioning

confidence: 99%

Accurate Detection of Urothelial Bladder Cancer Using Targeted Deep Sequencing of Urine DNA

Lee

Lee²,

Kim³

et al. 2023

Cancers

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Patients with hematuria are commonly given an invasive cystoscopy test to detect bladder cancer (BC). To avoid the risks associated with cystoscopy, several urine-based methods for BC detection have been developed, the most prominent of which is the deep sequencing of urine DNA. However, the current methods for urine-based BC detection have significant levels of false-positive signals. In this study, we report on uAL100, a method to precisely detect BC tumor DNA in the urine without tumor samples. Using urine samples from 43 patients with BC and 21 healthy donors, uAL100 detected BC with 83.7% sensitivity and 100% specificity. The mutations identified in the urine DNA by uAL100 for BC detection were highly associated with BC tumorigenesis and progression. We suggest that uAL100 has improved accuracy compared to other urine-based methods for early BC detection and can reduce unnecessary cystoscopy tests for patients with hematuria.

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Biomarkers of Bladder Cancer: Cell-Free DNA, Epigenetic Modifications and Non-Coding RNAs

Cited by 14 publications

References 139 publications

Comprehensive analysis reveals the value of the expression of chromobox family members for bladder urothelial carcinoma prognosis

Comprehensive analysis reveals the value of the expression of chromobox family members for bladder urothelial carcinoma prognosis

Evodiamine Exhibits Anti-Bladder Cancer Activity by Suppression of Glutathione Peroxidase 4 and Induction of Ferroptosis

Accurate Detection of Urothelial Bladder Cancer Using Targeted Deep Sequencing of Urine DNA

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