CDKN2A as transcriptomic marker for muscle-invasive bladder cancer risk stratification and therapy decision-making

Worst, Thomas; Weis, Cleo–Aron; Stöhr, Robert; Bertz, Simone; Eckstein, Markus; Otto, Wolfgang; Breyer, Johannes; Hartmann, Arndt; Bolenz, Christian; Wirtz, Ralph M.; Erben, Philipp

doi:10.1038/s41598-018-32569-x

Cited by 42 publications

(35 citation statements)

References 47 publications

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“…FGFR3-MA+KDM6A-MD and FGFR3-MA+CDKN2A-MD are the 1st and 3rd highest confidence GCRs in BLCA. The association between CDKN2A and prognosis is complicated in bladder cancer, as both p16 protein over-expression and complete lack of expression have been shown to be biomarkers of poor prognosis in bladder cancers [84,85]. In our study, CDKN2A deletion and CDKN2A mutations were combined into a single hybrid event, resulting in a simple association between CDKN2A-MD status and poor PFI ( Figure 9A).…”

Section: Cdkn2a and Fgfr3 Co-mutation Status Suggest A 3-tier Stratifmentioning

confidence: 78%

Identifying Modules of Cooperating Cancer Drivers

Klein

Cannataro

Townsend

et al. 2020

Preprint

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AbstractIdentifying cooperating modules of driver alterations can provide biological insights to cancer causation and would advance the development of effective personalized treatments. We present Cancer Rule-Set Optimization (CRSO) for inferring the combinations of alterations that cooperate to drive tumor formation in individual patients. Application to 19 TCGA cancer types found a mean of 11 core driver combinations per cancer, comprising 2-6 alterations per combination, and accounting for a mean of 70% of samples per cancer. CRSO departs from methods based on statistical cooccurrence, which we demonstrate is a suboptimal criterion for investigating driver cooperation. CRSO identified well-studied driver combinations that were not detected by other approaches and nominated novel combinations that correlate with clinical outcomes in multiple cancer types. Novel synergies were identified in NRAS-mutant melanomas that may be therapeutically relevant. Core driver combinations involving NFE2L2 mutations were identified in four cancer types, supporting the therapeutic potential of NRF2 pathway inhibition. CRSO is available at https://github.com/mikekleinsgit/CRSO/.

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Section: Cdkn2a and Fgfr3 Co-mutation Status Suggest A 3-tier Stratifmentioning

confidence: 78%

Identifying Modules of Cooperating Cancer Drivers

Klein

Cannataro

Townsend

et al. 2020

Preprint

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Section: Discussionmentioning

confidence: 51%

Upregulated CDKN2A expression may be an independent protective factor in Luminal-like breast cancer

Qiu¹,

Lu²,

Wu³

2020

Preprint

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Background: Previous studies revealed that CDKN2A (cyclin-dependent kinase inhibitor 2A) functioned as a tumour suppressor in various types of malignant tumours. The aim of the study was to clarify the value of CDKN2A expression in the prognosis of breast cancer.Method: Using the Cancer Genome Atlas (TCGA) database, we compared CDKN2A mRNA levels between breast cancer tissues and normal tissues and analyzed the relationship between clinical features and CDKN2A expression with the Wilcox test and the Kruskal-Wallis test. Kaplan-Meier and Cox analyses were performed to determine the correlation between CDKN2A expression and breast cancer prognosis. Gene set enrichment analysis (GSEA) was performed using the TCGA data set.Results: We first found that CDKN2A expression was markedly higher in breast cancer tissues than in normal tissues using the TCGA database (P=0.000). In addition, CDKN2A mRNA expression in breast cancer was positively correlated with age (P=0.018), histological types (P=0.028), ER status (P=0.000), PR status (P=0.000) and molecular subtypes (P=0.000). Kaplan-Meier analysis showed that increased CDKN2A expression was associated with increased survival time in breast cancer patients (P=0.000), especially in Luminal-like subtype. Univariate and multivariate Cox analyses indicated that CDKN2A expression was an independent prognostic biomarker for breast cancer (P=0.037). GSEA suggested that pathways involving cell adhesion molecules (CAMs), cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity were differentially enriched in the CDKN2A-high expression group.Conclusion: Our research demonstrated that high CDKN2A mRNA expression was an independent protective factor for improved prognosis in Luminal-like breast cancer. Additionally, the signaling pathways related to CAMs, cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity regulated by CDKN2A mRNA expression should be further studied.

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“…Meanwhile, another study pointed out that cancer gene therapy mediated by CDKN2A was bene cial for the induction of cell death in non-smallcell lung carcinoma [20]. In addition, we found CDKN2A mRNA expression was associated with bladder cancer, the cell cycle and DNA replication [27][28][29]. However, it is the rst time that the results in this paper showing correlations between CDKN2A expression and signalling pathways involving CAMs, cytokinereceptor interactions, cytosolic DNA sensing and killer cell-mediated cytotoxicity are reported, as well as biological mechanism needs to be further clari ed.…”

Section: Discussionmentioning

confidence: 58%

Upregulated CDKN2A expression may be an independent protective factor in Luminal-like breast cancer

Qiu¹,

Lu²,

Wu³

2020

Preprint

View full text Add to dashboard Cite

Background Previous studies revealed that CDKN2A (cyclin-dependent kinase inhibitor 2A) functioned as a tumour suppressor in various types of malignant tumours. The aim of the study was to clarify the value of CDKN2A expression in the prognosis of breast cancer. Method Using the Cancer Genome Atlas (TCGA) database, we compared CDKN2A mRNA levels between breast cancer tissues and normal tissues and analyzed the relationship between clinical features and CDKN2A expression with the Wilcox test and the Kruskal-Wallis test. Kaplan-Meier and Cox analyses were performed to determine the correlation between CDKN2A expression and breast cancer prognosis. Gene set enrichment analysis (GSEA) was performed using the TCGA data set. Results We first found that CDKN2A expression was markedly higher in breast cancer tissues than in normal tissues using the TCGA database (P=0.000). In addition, CDKN2A mRNA expression in breast cancer was positively correlated with age (P=0.018), histological types (P=0.028), ER status (P=0.000), PR status (P=0.000) and molecular subtypes (P=0.000). Kaplan-Meier analysis showed that increased CDKN2A expression was associated with increased survival time in breast cancer patients (P=0.000), especially in Luminal-like subtype. Univariate and multivariate Cox analyses indicated that CDKN2A expression was an independent prognostic biomarker for breast cancer (P=0.037). GSEA suggested that pathways involving cell adhesion molecules (CAMs), cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity were differentially enriched in the CDKN2A-high expression group. Conclusion Our research demonstrated that high CDKN2A mRNA expression was an independent protective factor for improved prognosis in Luminal-like breast cancer. Additionally, the signaling pathways related to CAMs, cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity regulated by CDKN2A mRNA expression should be further studied.

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CDKN2A as transcriptomic marker for muscle-invasive bladder cancer risk stratification and therapy decision-making

Cited by 42 publications

References 47 publications

Identifying Modules of Cooperating Cancer Drivers

Identifying Modules of Cooperating Cancer Drivers

Upregulated CDKN2A expression may be an independent protective factor in Luminal-like breast cancer

Upregulated CDKN2A expression may be an independent protective factor in Luminal-like breast cancer

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