The Prognostic Role of CDK9 in Bladder Cancer

Borowczak, Jędrzej; Szczerbowski, Krzysztof; Maniewski, Mateusz; Zdrenka, Marek; Słupski, Piotr; Antosik, Paulina; Kołodziejska, Sylwia; Sekielska-Domanowska, Marta I; Dubiel, Mariusz; Bodnar, Magdalena; Szylberg, Łukasz

doi:10.3390/cancers14061492

Cited by 9 publications

(8 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…f Relative wound healing area was lower in Si-LAMA2 group than that in NC group same tendency as the 7 genes in the prognostic model. Borowczak J et al reported CDK9 in bladder cancer via the HPA database [48]. The functional experiments successfully verified that COL6A1 promoted the migration of bladder cancer cells as a risk factor, and bladder cancer cells were down-regulated after knocking down the expression of COL6A1.…”

Section: Discussionmentioning

confidence: 90%

A novel focal adhesion-related risk model predicts prognosis of bladder cancer —— a bioinformatic study based on TCGA and GEO database

Wang

et al. 2022

BMC Cancer

View full text Add to dashboard Cite

Background Bladder cancer (BLCA) is the ninth most common cancer globally, as well as the fourth most common cancer in men, with an incidence of 7%. However, few effective prognostic biomarkers or models of BLCA are available at present. Methods The prognostic genes of BLCA were screened from one cohort of The Cancer Genome Atlas (TCGA) database through univariate Cox regression analysis and functionally annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The intersecting genes of the BLCA gene set and focal adhesion-related gene were obtained and subjected to the least absolute shrinkage and selection operator regression (LASSO) to construct a prognostic model. Gene set enrichment analysis (GSEA) of high- and low-risk patients was performed to explore further the biological process related to focal adhesion genes. Univariate and multivariate Cox analysis, receiver operating characteristic (ROC) curve analysis, and Kaplan–Meier survival analysis (KM) were used to evaluate the prognostic model. DNA methylation analysis was presented to explore the relationship between prognosis and gene methylation. Furthermore, immune cell infiltration was assessed by CIBERSORT, ESTIMATE, and TIMER. The model was verified in an external GSE32894 cohort of the Gene Expression Omnibus (GEO) database, and the Prognoscan database presented further validation of genes. The HPA database validated the related protein level, and functional experiments verified significant risk factors in the model. Results VCL, COL6A1, RAC3, PDGFD, JUN, LAMA2, and ITGB6 were used to construct a prognostic model in the TCGA-BLCA cohort and validated in the GSE32894 cohort. The 7-gene model successfully stratified the patients into both cohorts’ high- and low-risk groups. The higher risk score was associated with a worse prognosis. Conclusions The 7-gene prognostic model can classify BLCA patients into high- and low-risk groups based on the risk score and predict the overall survival, which may aid clinical decision-making.

show abstract

Section: Discussionmentioning

confidence: 90%

A novel focal adhesion-related risk model predicts prognosis of bladder cancer —— a bioinformatic study based on TCGA and GEO database

Wang

et al. 2022

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…Moreover, high CDK9 expression measured immunohistochemically correlated with longer patient survival. Those results were subsequently confirmed in The Cancer Genome Atlas cohort [22]. On the contrary, in Antonova et al Study, CDK9 was upregulated in muscle-invasive bladder cancer samples when compared to non-muscle-invasive samples [45].…”

Section: The Role Of Cdk9 In Urothelial Carcinomamentioning

confidence: 83%

“…The patients were dichotomized into low and high-expression groups. In the TCGA cohort, high CDK9 expression correlated with longer overall survival and favorable clinical features of urothelial carcinoma [ 22 ]. We found that tumors with no lymph node metastasis showed higher TP53 levels than those with lymph node metastasis (median FPKM 21.35 vs 18.00; p < 0.05) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In the early stages of BLCA, the overexpression of CDK9 and p53 seems to be a common occurrence. However, even in bladder cancers with high CDK9 expression, which seems to be a feature of less aggressive disease, high expression of p53 is associated with muscle-invasive, high-grade and metastatic cancers [ 22 ]. Those results suggest an interplay between CDK9 and p53, which may affect the progression of the disease, especially in its early stages.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The prognostic role of p53 and its correlation with CDK9 in urothelial carcinoma

et al. 2022

Self Cite

View full text Add to dashboard Cite

Purpose The mutation of p53 is considered a pivotal step in bladder cancer pathogenesis. Recently, distinct interactions between p53 and CDK9, a transcription regulator, have been described. In this work, we explored the prognostic role of p53 expression and evaluated its associations with CDK9 in urothelial carcinoma. Materials and methods The research group consisted of 67 bladder cancer samples and 32 normal urothelial mucosa samples. All specimens were analyzed using ImageJ and the IHC profiler plugin. To validate the results, 406 cases from The Cancer Genome Atlas database were analyzed. Results P53 and CDK9 are overexpressed in urothelial cancer tissues when compared to normal urothelial tissues (p < 0.05). High p53 expression was observed in metastatic tumors and tumors with high CDK9 expression (p < 0,05). High p53 expression was predictive for shorter survival in patients with non-muscle-invasive bladder cancer (HR = 0.107 [0.012–0.96]; p = 0.046) but did not correlate with prognosis in the muscle-invasive group. In high CDK9 cancers, high p53 expression correlated with the occurrence of high-grade and muscle-invasive tumors (p < 0.05). Conclusion High expression of p53 correlates with unfavorable clinical features of bladder cancer. CDK9 is associated with the expression of p53, possibly through interactions with p53 inhibitors. Since the blockade of CDK9 in other malignancies reactivates wild-p53 activity, confirming the crosstalk between p53 and CDK9 in bladder cancer may be another step to explain the mechanism of tumor progression in its early stages.

show abstract

“…As for caspase-8, the prognostic/predictive value of CDK9, however, still remains controversial among different tumor types. Whereas some authors have indicated that high levels of CDK9 expression in patients with pancreatic adenocarcinoma are associated with significantly shortened OS, especially in well differentiated tumors [ 36 , 41 , 42 ], others have demonstrated that higher CDK9 expression is associated with significantly improved survival [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of Caspase-8, CDK9 and Phospho-CDK9 (Thr 186) Expression in Patients with Uterine Cervical Cancer Treated with Definitive Chemoradiation and Brachytherapy

Fleischmann

Mandal

Kostova

et al. 2022

Cancers

View full text Add to dashboard Cite

Introduction: After primary platinum-based chemoradiation of locally advanced uterine cervical cancer, a substantial proportion of women present with persistent, recurrent or metastatic disease, indicating an unmet need for biomarker development. Methods: We evaluated the clinical records of 69 cervical cancer patients (Federation of Gynecology and Obstetrics, FIGO Stage > IB3) who were subjected to definitive CRT. Immunohistochemical scoring of caspase-8, cyclin dependent kinase 9 (CDK9) and phosphorylated (phospho-)CDK9 (threonine (Thr) 186) was performed on pretreatment samples and correlated with the histopathological and clinical endpoints, including relapse-free survival (RFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS) and overall survival (OS). Results: Lower levels of caspase-8 were more prevalent in patients with a higher T-stage (p = 0.002) and a higher FIGO stage (p = 0.003), and were significantly correlated with CDK9 expression (p = 0.018) and inversely with pCDK9 detection (p = 0.014). Increased caspase-8 levels corresponded to improved RFS (p = 0.005), DMFS (p = 0.038) and CSS (p = 0.017) in the univariate analyses. Low CDK9 expression was associated with worse RFS (p = 0.008), CSS (p = 0.015) and OS (p = 0.007), but not DMFS (p = 0.083), and remained a significant prognosticator for RFS (p = 0.003) and CSS (p = 0.009) in the multivariate analyses. Furthermore, low pCDK9 staining was significantly associated with superior RFS (p = 0.004) and DMFS (p = 0.001), and increased CSS (p = 0.022), and remained significant for these endpoints in the multivariate analyses. Conclusion: Increased caspase-8 and CDK9 levels correlate with improved disease-related outcomes in cervical cancer patients treated with CRT, whereas elevated pCDK9 levels predict worse survival in this patient population.

show abstract

The Prognostic Role of CDK9 in Bladder Cancer

Cited by 9 publications

References 51 publications

A novel focal adhesion-related risk model predicts prognosis of bladder cancer —— a bioinformatic study based on TCGA and GEO database

A novel focal adhesion-related risk model predicts prognosis of bladder cancer —— a bioinformatic study based on TCGA and GEO database

The prognostic role of p53 and its correlation with CDK9 in urothelial carcinoma

Prognostic Impact of Caspase-8, CDK9 and Phospho-CDK9 (Thr 186) Expression in Patients with Uterine Cervical Cancer Treated with Definitive Chemoradiation and Brachytherapy

Contact Info

Product

Resources

About