Research Article

Drug repurposing analysis with co-expressed genes identifies novel drugs and small molecules for bladder cancer

Number: 056 March 31, 2024
EN

Drug repurposing analysis with co-expressed genes identifies novel drugs and small molecules for bladder cancer

Abstract

Bladder cancer (BC) is the fifth most common malignancy in humans and has poor survival rates. Although there is extensive research on the diagnosis and treatment of BC, novel molecular therapies are essential due to tumor recurrence. In this study, we aim to identify repurposed drugs or small molecules of BC with multi-omics systems biology perspective. Gene expression datasets were statistically analyzed by comparing bladder tumor and normal bladder tissues and differentially expressed genes (DEGs) were determined. Co-expression network of common DEGs for BC was constructed and co-expressed module was found by using tumors and control bladder tissues. Using independent data, we demonstrated the high prognostic capacity of the module genes. Moreover, repurposed drugs or small molecules were predicted by using L1000CDS2 gene expression based-search engine tool. We found numerous drug candidates as 480743.cdx, MK-2206, Geldanamycin, PIK-90, BRD-K50387473 (XMD8-92), BRD-K96144918 (mead acid), Vorinostat, PLX-4720, Entinostat, BIX-01294, PD-0325901 and Selumetinib, that may be used in BC therapy. We report 480743.cdx, BRD-K50387473 (XMD8-92) and mead acid as novel drugs or small molecules that offer crucial step in translational cancer research of BC.

Keywords

Ethical Statement

Not applicable.

References

  1. [1] Tang, C., Yu, M., Ma, J., and Zhu, Y, “Metabolic classification of bladder cancer based on multi‑omics integrated analysis to predict patient prognosis and treatment response”, J Transl Med, vol. 19 no. 205, 2021, doi: 10.1186/s13073-022-01056-4.
  2. [2] Yu, E.Y.-W., Zhang, H., Fu Y., et al, “Integrative multi-omics analysis for the determination of non-muscle invasive vs. muscle invasive bladder cancer: a pilot study”, Curr Oncol, vol. 29, no. 8, pp. 5442–5456, 2022, doi: 10.3390/curroncol29080430.
  3. [3] Mo, Q., Li, R, Adeegbe, D.O., Peng, G., and Chan, K.S., “Integrative multi-omics analysis of muscle-invasive bladder cancer identifies prognostic biomarkers for frontline chemotherapy and immunotherapy”, Commun Bıol. Vol. 3, no. 784, 2020, doi:10.1038/s42003-020-01491-2.
  4. [4] Lindskrog, S.V., Prip, F., Lamy, P., et al., “An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle invasive bladder cancer.”, Nat Commun., vol. 12, no. 2301, 2021. doi: 10.1038/s41467-021-22465-w.
  5. [5] Shi, Z.-D. Han, X.-X., Song, Z.-J., et al., “Integrative multi‑omics analysis depicts the methylome and hydroxymethylome in recurrent bladder cancers and identifies biomarkers for predicting PD‑L1 expression.”, Biomark. Res., vol. 11, no. 47, 2023, doi: 10.1186/s40364-023-00488-3.
  6. [6] Zhang, X., Wang, J., Lu, J. et al., “Robust prognostic subtyping of muscle-invasive bladder cancer revealed by deep learning-based multi-omics data integration”, Front. Oncol., vol. 11, no. 689626, 2021, doi.org/10.3389/fonc.2021.689626.
  7. [7] You, C., Piao, X.M., Kang, K., Kim, Y.J., and Kang, K., “Integrative transcriptome profiling reveals ska3 as a novel prognostic marker in non-muscle invasive bladder cancer.”, Cancers, vol. 13, no. 18, 4673, 2021, doi: 10.3390/cancers13184673.
  8. [8] Demirtas, T.Y., Rahman, R., Capkin Yurtsever, M., and Gov, E., “Forecasting gastric cancer diagnosis, prognosis, and drug repurposing with novel gene expression signatures.”, OMICS A J. Integr. Biol., vol. 26, no. 1, 2022, DOI:10.1089/omi.2021.0195.

Details

Primary Language

English

Subjects

Gene and Molecular Therapy, Medical Biotechnology Diagnostics, Bioengineering (Other)

Journal Section

Research Article

Publication Date

March 31, 2024

Submission Date

November 28, 2023

Acceptance Date

February 1, 2024

Published in Issue

Year 2024 Number: 056

APA
Göv, E., & Kaynak Bayrak, G. (2024). Drug repurposing analysis with co-expressed genes identifies novel drugs and small molecules for bladder cancer. Journal of Scientific Reports-A, 056, 70-81. https://doi.org/10.59313/jsr-a.1397224
AMA
1.Göv E, Kaynak Bayrak G. Drug repurposing analysis with co-expressed genes identifies novel drugs and small molecules for bladder cancer. JSR-A. 2024;(056):70-81. doi:10.59313/jsr-a.1397224
Chicago
Göv, Esra, and Gökçe Kaynak Bayrak. 2024. “Drug Repurposing Analysis With Co-Expressed Genes Identifies Novel Drugs and Small Molecules for Bladder Cancer”. Journal of Scientific Reports-A, nos. 056: 70-81. https://doi.org/10.59313/jsr-a.1397224.
EndNote
Göv E, Kaynak Bayrak G (March 1, 2024) Drug repurposing analysis with co-expressed genes identifies novel drugs and small molecules for bladder cancer. Journal of Scientific Reports-A 056 70–81.
IEEE
[1]E. Göv and G. Kaynak Bayrak, “Drug repurposing analysis with co-expressed genes identifies novel drugs and small molecules for bladder cancer”, JSR-A, no. 056, pp. 70–81, Mar. 2024, doi: 10.59313/jsr-a.1397224.
ISNAD
Göv, Esra - Kaynak Bayrak, Gökçe. “Drug Repurposing Analysis With Co-Expressed Genes Identifies Novel Drugs and Small Molecules for Bladder Cancer”. Journal of Scientific Reports-A. 056 (March 1, 2024): 70-81. https://doi.org/10.59313/jsr-a.1397224.
JAMA
1.Göv E, Kaynak Bayrak G. Drug repurposing analysis with co-expressed genes identifies novel drugs and small molecules for bladder cancer. JSR-A. 2024;:70–81.
MLA
Göv, Esra, and Gökçe Kaynak Bayrak. “Drug Repurposing Analysis With Co-Expressed Genes Identifies Novel Drugs and Small Molecules for Bladder Cancer”. Journal of Scientific Reports-A, no. 056, Mar. 2024, pp. 70-81, doi:10.59313/jsr-a.1397224.
Vancouver
1.Esra Göv, Gökçe Kaynak Bayrak. Drug repurposing analysis with co-expressed genes identifies novel drugs and small molecules for bladder cancer. JSR-A. 2024 Mar. 1;(056):70-81. doi:10.59313/jsr-a.1397224