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. 2022 Feb 7;159(1):13.
doi: 10.1186/s41065-021-00212-x.

Identification of a chromatin regulator signature and potential candidate drugs for bladder cancer

Ke Zhu #  1 , Xiaoqiang Liu #  1 , Wen Deng #  1 , Gongxian Wang  2   3 , Bin Fu  4   5
Affiliations

Identification of a chromatin regulator signature and potential candidate drugs for bladder cancer

Ke Zhu et al. Hereditas. .

Abstract

Background: Bladder cancer (BLCA) is a malignant tumor with a dismay outcome. Increasing evidence has confirmed that chromatin regulators (CRs) are involved in cancer progression. Therefore, we aimed to explore the function and prognostic value of CRs in BLCA patients.

Methods: Chromatin regulators (CRs) were acquired from the previous top research. The mRNA expression and clinical information were downloaded from TCGA and GEO datasets. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were performed to select the prognostic gene and construct the risk model for predicting outcome in BLCA. The Kaplan-Meier analysis was used to assess the prognosis between high- and low-risk groups. We also investigated the drug sensitivity difference between high- and low-risk groups. CMAP dataset was performed to screen the small molecule drugs for treatment.

Results: We successfully constructed and validated an 11 CRs-based model for predicting the prognosis of patients with BLCA. Moreover, we also found 11 CRs-based model was an independent prognostic factor. Functional analysis suggested that CRs were mainly enriched in cancer-related signaling pathways. The CR-based model was also correlated with immune cells infiltration and immune checkpoint. Patients in the high-risk group were more sensitive to several drugs, such as mitomycin C, gemcitabine, cisplatin. Eight small molecule drugs could be beneficial to treatment for BLCA patients.

Conclusion: In conclusion, our study provided novel insights into the function of CRs in BLCA. We identified a reliable prognostic biomarker for the survival of patients with BLCA.

Keywords: Bladder cancer; Chromatin regulators; Prognosis; TCGA.

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Conflict of interest statement

No competing interests.

Figures

Figure 1
Figure 1
Heatmap showed differentially expressed CRs
Figure 2
Figure 2
Identification of prognostic CRs by univariate Cox regression analysis
Figure 3
Figure 3
Construction of the prognostic CR-based signature in TCGA set. A. Kaplan-Meier survival analysis of BLCA patients between high-risk groups and low-risk groups in TCGA set; B. Time-independent receiver operating characteristic (ROC) analysis of risk scores predicting the overall survival in TCGA set; C. Distribution of survival status based on the median risk score in TCGA set; D. Heatmap showed the differences of 11 chromatin regulators between high and low-risk patients in TCGA set
Figure 4
Figure 4
Validation of the prognostic CR-based signature in the GSE13507 set. A. Kaplan-Meier survival analysis of BLCA patients between high-risk groups and low-risk groups in GSE13507 set; B. Time-independent receiver operating characteristic (ROC) analysis of risk scores predicting the overall survival in GSE13507 set; C. Distribution of survival status based on the median risk score in GSE13507 set; D. Heatmap showed the differences of 11 chromatin regulators between high and low-risk patients in GSE13507 set
Figure 5
Figure 5
The signature was an independent prognostic factor for BLCA in the TCGA set. (A) The correlations between the risk score for OS and clinicopathological factors by univariate Cox regression analysis; (B) The correlations between the risk score for OS and clinicopathological factors by multivariate Cox regression analysis
Figure 6
Figure 6
Correlation between signature and clinical characteristics
Figure 7
Figure 7
Kaplan-Meier curves of OS differences stratified by gender, age, grade, N stage, T stage, or TNM stage between the high-risk groups and low-risk groups
Figure 8
Figure 8
Construction of a nomogram. (A) nomogram for predicting 3- or 5-year OS; (B) The calibration plots for predicting 3-year OS; (C) The calibration plots for predicting 5-year OS
Figure 9
Figure 9
Enrichment analyses of differentially expressed CRs. (A) GO analysis; (B) KEGG analysis
Figure 10
Figure 10
Protein-protein interaction network of differentially expressed CRs
Figure 11
Figure 11
GSEA analysis
Figure 12
Figure 12
Immune cells infiltration between high-risk groups and low-risk groups
Figure 13
Figure 13
The relationship between prognostic signature and immune checkpoints
Figure 14
Figure 14
Drug sensitivity analysis
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References

    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA. Cancer J. Clin. 2021;71:7–33. doi: 10.3322/caac.21654. - DOI - PubMed
    1. Wen J, Yang T, Mallouk N, Zhang Y, Li H, Lambert C, Li G. Urinary Exosomal CA9 MRNA as a Novel Liquid Biopsy for Molecular Diagnosis of Bladder Cancer. Int. J. Nanomedicine. 2021;16:4805–4811. doi: 10.2147/IJN.S312322. - DOI - PMC - PubMed
    1. Piao X-M, Cha E-J, Yun SJ, Kim W-J. Role of Exosomal MiRNA in Bladder Cancer: A Promising Liquid Biopsy Biomarker. Int. J. Mol. Sci. 2021;22:1713. doi: 10.3390/ijms22041713. - DOI - PMC - PubMed
    1. Iyer G, Rosenberg JE. Novel Therapies in Urothelial Carcinoma: A Biomarker-Driven Approach. Ann. Oncol. 2018;29:2302–2312. doi: 10.1093/annonc/mdy254. - DOI - PMC - PubMed
    1. Ghasemzadeh A, Bivalacqua TJ, Hahn NM, Drake CG. New Strategies in Bladder Cancer: A Second Coming for Immunotherapy. Clin. Cancer Res. 2016;22:793–801. doi: 10.1158/1078-0432.CCR-15-1135. - DOI - PMC - PubMed