Variations in Circulating Tumor Microenvironment-Associated Proteins in Non-Muscle Invasive Bladder Cancer Induced by Mitomycin C Treatment

TL;DR

This study identifies changes in proteins linked to the tumor environment in bladder cancer patients treated with Mitomycin C, revealing potential biomarkers for treatment response.

Contribution

The study introduces a novel nanoproteomic strategy to identify a tumor microenvironment proteomic signature associated with Mitomycin C treatment response in bladder cancer.

Findings

Prothrombin (F2) was downregulated in all patients during Mitomycin C treatment.

Complement component C7 (C7) was upregulated in all patients during treatment.

These findings suggest immune response proteins could serve as biomarkers for treatment outcomes.

Abstract

Mitomycin C (MMC) is a widely employed chemotherapeutic agent, particularly in non-muscle invasive bladder cancer (NMIBC), where it functions by inducing DNA cross-linking and promoting tumor cell apoptosis. However, the tumor microenvironment (TME) significantly influences the therapeutic efficacy of MMC. Among the key regulators within the TME, the complement system and the coagulation pathway play a crucial role in modulating immune responses to cancer therapies, including MMC. This article explores the interaction between platinum nanoparticles (PtNPs) with human serum (HS) of NMIBC patients (T1 and Ta subtypes) at three different points: before the chemotherapy instillation of MMC (t0) and three (t3) and six months (t6) after the treatment with MMC. This novel nanoproteomic strategy allowed the identification of a TME proteomic signature associated with the response to MMC treatment. Importantly, two proteins involved in the immune response were found to be deregulated across all patients (T1 and Ta subtypes) during MMC treatment: prothrombin (F2) downregulated and complement component C7 (C7) upregulated. By understanding how these biomarker proteins interact with MMC treatment, novel therapeutic strategies can be developed to enhance treatment outcomes and overcome resistance in NMIBC.

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