# Identification of SCAMP2 as a regulator of NOTCH signaling in cisplatin resistance through a novel prognostic model for bladder cancer

## TL;DR

This study identifies SCAMP2 as a key gene involved in cisplatin resistance in bladder cancer, offering a new prognostic model and potential therapeutic target.

## Contribution

The study introduces a novel prognostic model using CSRGs and identifies SCAMP2 as a regulator of NOTCH signaling in cisplatin resistance.

## Key findings

- The prognostic model showed high AUC values and strong predictive performance for bladder cancer outcomes.
- SCAMP2 overexpression enhances cisplatin sensitivity in bladder cancer tissues via NOTCH signaling.
- SCAMP2 is strongly correlated with sensitivity to multiple anti-cancer drugs, including cisplatin.

## Abstract

Bladder cancer remains a major challenge in clinical oncology, particularly due to the development of platinum resistance, which severely impacts patient prognosis. Despite numerous attempts to create effective prognostic models, their clinical applicability has often been limited.

In this study, we utilized a robust statistical approach, LASSO-COX regression analysis, to develop a novel prognostic model for bladder cancer based on cisplatin sensitivity-related genes (CSRGs). The model was validated using both the TCGA-BLCA dataset and an independent validation set, GSE32894. Additionally, we employed various in vitro assays, including CCK-8 and EdU assays for cell proliferation, transwell assays for migration, and flow cytometry for apoptosis analysis, to investigate the biological function of the identified genes.

Our prognostic model demonstrated superior predictive performance, with high AUC values. SCAMP2 was identified as a critical gene with elevated expression in bladder cancer, showing strong correlation with sensitivity to multiple anti-cancer drugs, including cisplatin. Further functional assays revealed that SCAMP2 mediates drug resistance in bladder cancer cells via the NOTCH signaling pathway. Additionally, in vivo experiments showed that SCAMP2 overexpression significantly enhanced cisplatin sensitivity in bladder cancer tissues.

These findings underscore the potential of CSRGs, particularly SCAMP2, as critical biomarkers for bladder cancer prognosis. The identification of SCAMP2 as a regulator of NOTCH signaling in cisplatin resistance offers new insights into the molecular mechanisms of chemotherapy resistance and suggests potential therapeutic targets for overcoming drug resistance. Our model could guide personalized treatment strategies and improve bladder cancer patient outcomes.