Integrating Genomic and Pharmacological Insights to Enhance Bladder Cancer and COVID-19 Treatment

The COVID-19 pandemic has undoubtedly emerged as one of the most significant global public health challenges in modern history.

Treatments for COVID-19 have included antiviral agents, neutralizing antibody therapies, and hormonotherapy, yet a specific medicine designed exclusively for treating this disease remains elusive .

Concurrently, malignant tumors, particularly bladder cancer, continue to pose a formidable clinical challenge worldwide, with bladder cancer ranking as one of the leading causes of tumor-induced mortality .

Despite the presence of individual variations and drug tolerance, immunotherapy has remained a potent clinical treatment strategy for patients battling bladder cancer.

Bladder cancer patients, especially those in advanced stages, often exhibit alterations in immune cell components following extended chemotherapy, leading to immune dysregulation and an increased potential for tumorigenesis, including bladder cancer itself.

Furthermore, interactions between tumor therapy actions affecting immune function and chronic comorbidities induced by COVID-19 can result in higher risks of severe outcomes for cancer patients. This interplay between bladder cancer and COVID-19 underscores the vulnerability of bladder cancer patients to SARS-CoV-2 infection during the pandemic, potentially compromising clinical treatment efficacy and reducing overall survival durations.

This study aims to shed light on the molecular connections between bladder cancer and COVID-19, offering insights into potential therapeutic strategies that could enhance the treatment of both conditions. Through the identification of differentially expressed genes (DEGs) in bladder cancer and the intersection of genes common to both bladder cancer and COVID-19, we have constructed a risk score using 21 risk factors correlated with clinical phenotypes and gene expression characteristics in bladder cancer patients.

These findings can be used to develop prognostic models for bladder cancer patients, assess their risk of death, and evaluate therapeutic efficiency.

Risk Assessment and Prognostic Analysis

Our comprehensive analysis revealed that higher risk scores were associated with increased death rates and risk in bladder cancer patients. This observation underscores the utility of risk scores as predictive tools for clinical outcomes in bladder cancer cases. Additionally, these risk scores have shown promise in assessing the therapeutic efficiency of treatments for bladder cancer.

The identification of 21 gene expressions significantly associated with the overall survival of bladder cancer patients suggests that these genes may serve as potential diagnostic markers for both bladder cancer and COVID-19.

These markers hold the potential to revolutionize the early diagnosis and management of these conditions, improving patient outcomes.

Dimensionality Reduction Analysis and Network Pharmacology

Dimensionality reduction analysis, represented by principal component analysis (PCA) maps, illustrated the distribution of risk-signature genes across gene expression profiles of bladder cancer patients.

This analysis revealed significant dispersion between high-risk and low-risk groups, emphasizing the potential clinical relevance of these risk signatures.

Furthermore, network pharmacology analysis identified ten core targets of pachymic acid against bladder cancer and COVID-19.

Functional enrichment visualization revealed that pachymic acid may play a role in regulating the tumor microenvironment and reducing cell proliferation in the context of bladder cancer and COVID-19.

Additionally, the analysis indicated that pachymic acid might be associated with molecular immunology regulation and inhibition of viral activity, suggesting its potential utility in treating both conditions.

Molecular Docking Analysis

Molecular docking analysis identified key targeting proteins, including CCL2, THBS1, and MMP1. CCL2, a critical chemotactic gene, has been implicated in bladder cancer progression and is associated with immunosuppressive microenvironments and tumor angiogenesis. THBS1, a cell adhesion molecule, plays vital roles in inhibiting angiogenesis, modulating antitumor immunity, and controlling tumor cell migration. MMP1, an activator of protease activated receptor-1, is involved in oncogenesis and metastasis in various cancers. Importantly, these proteins have been associated with COVID-19 severity.

Conclusion

In conclusion, this study has provided valuable insights into the intricate relationship between bladder cancer and COVID-19, highlighting the vulnerability of bladder cancer patients during the pandemic and the potential for shared therapeutic strategies. The identification of risk signatures, prognostic markers, and pharmacological targets offers a promising avenue for improving the diagnosis and treatment of bladder cancer and COVID-19.

However, it is essential to acknowledge the limitations of this study. The risk assessment score was determined retrospectively, necessitating further clinical validation. Moreover, the pharmacological biotargets identified through network pharmacology and molecular docking analyses require experimental confirmation before potential clinical applications can be considered. Despite these limitations, the findings presented here provide a foundation for future research and the development of innovative therapeutic approaches for bladder cancer and COVID-19.

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reference link : https://www.tandfonline.com/doi/full/10.1080/10942912.2023.2252194