Prediction of anticancer drug resistance using a 3D microfluidic bladder cancer model combined with convolutional neural network-based image analysis

Front Bioeng Biotechnol. 2024 Jan 10:11:1302983. doi: 10.3389/fbioe.2023.1302983. eCollection 2023.

Abstract

Bladder cancer is the most common urological malignancy worldwide, and its high recurrence rate leads to poor survival outcomes. The effect of anticancer drug treatment varies significantly depending on individual patients and the extent of drug resistance. In this study, we developed a validation system based on an organ-on-a-chip integrated with artificial intelligence technologies to predict resistance to anticancer drugs in bladder cancer. As a proof-of-concept, we utilized the gemcitabine-resistant bladder cancer cell line T24 with four distinct levels of drug resistance (parental, early, intermediate, and late). These cells were co-cultured with endothelial cells in a 3D microfluidic chip. A dataset comprising 2,674 cell images from the chips was analyzed using a convolutional neural network (CNN) to distinguish the extent of drug resistance among the four cell groups. The CNN achieved 95.2% accuracy upon employing data augmentation and a step decay learning rate with an initial value of 0.001. The average diagnostic sensitivity and specificity were 90.5% and 96.8%, respectively, and all area under the curve (AUC) values were over 0.988. Our proposed method demonstrated excellent performance in accurately identifying the extent of drug resistance, which can assist in the prediction of drug responses and in determining the appropriate treatment for bladder cancer patients.

Keywords: bladder cancer; convolutional neural network; drug resistance; organ-on-a-chip; step decay learning rate.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants (2022R1A2C2003757 and 2022R1F1A1074729) from the National Research Foundation of Korea (NRF) funded by the Korean Government (MSIT), and grants (D300500 and C318300) from the Korea Basic Science Institute.