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Research ArticleClinical Studies
Open Access

Transcriptome-based Deep Learning Model for Predicting Gemcitabine and Cisplatin Chemotherapy Response in Urothelial Carcinoma: Development and External Validation

JUWON KANG, HYUN JUNG LEE, SANG-BO OH, JONG KIL NAM, TAE UN KIM, HWASEONG RYU, YONG KAN KI, JIHOON KANG, YI RANG KIM, JEONG HOON LEE, JUNJEONG CHOI, YUN JEONG HONG and KWONOH PARK
Cancer Genomics & Proteomics May 2026, 23 (3) 546-557; DOI: https://doi.org/10.21873/cgp.20589
JUWON KANG
1ONCOCROSS Co., Ltd., Seoul, Republic of Korea;
2Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, Republic of Korea;
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HYUN JUNG LEE
3Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea;
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SANG-BO OH
4Medical Oncology and Hematology, Department of Internal medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea;
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JONG KIL NAM
5Department of Urology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea;
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TAE UN KIM
6Department of Radiology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea;
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HWASEONG RYU
6Department of Radiology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea;
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YONG KAN KI
7Department of Radiation Oncology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea;
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JIHOON KANG
1ONCOCROSS Co., Ltd., Seoul, Republic of Korea;
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YI RANG KIM
1ONCOCROSS Co., Ltd., Seoul, Republic of Korea;
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JEONG HOON LEE
8Department of Radiology, Stanford University School of Medicine, Stanford, CA, U.S.A.;
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JUNJEONG CHOI
2Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, Republic of Korea;
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YUN JEONG HONG
9Department of Neurology, Uijeongbu St. Mary’s Hospital, Catholic University of Korea, Seoul, Republic of Korea;
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KWONOH PARK
3Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea;
10Division of Hematology & Medical Oncology, Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Republic of Korea
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  • For correspondence: parkkoh{at}daum.net
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    Figure 1.

    Overview of the study design and analytical workflow. Schematic representation of the study workflow. Bladder cancer cases with gemcitabine and cisplatin response data were collected from three sources: TCGA-BLCA (n=81), GSE247185 (n=13), and PNUYH (n=10). Gene expression data from TCGA and GSE datasets underwent quantification and augmentation to create the training dataset (12,961 genes, n=4,794), which was used to develop a 5-layer fully connected neural network for drug response classification. The PNUYH cohort served as an independent external validation set. The model was evaluated through internal validation, external validation, biological interpretation of predictive features, and survival analysis. PNUYH: Pusan National University Yangsan Hospital; TCGA-BLCA: the Cancer Genome Atlas Bladder Cancer cohort.

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    Figure 2.

    Performance evaluation of the deep learning model in internal and external validation. (A-C) Internal validation results: (A) ROC curves are presented for the training and internal validation sets; (B) Training and validation loss curves over 200 epochs showing stable convergence; (C) Precision, recall, and F1-score metrics across different threshold values with optimal threshold (0.4) indicated by the vertical dashed line. (D-G) External validation results: (D) ROC curves for training and external test sets with respective AUROCs; (E) Loss curves during external validation showing good generalization; (F) Detailed performance metrics for each fold during 5-fold cross-validation; (G) Final performance metrics and confusion matrix of the model in training and external validation datasets. AUROC: Area under the receiver operating characteristic curve; ROC, receiver operating characteristic.

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    Figure 3.

    Gene ontology enrichment analysis of chemotherapy response-associated genes. (A) Bar plots showing enriched biological process terms in four major functional clusters. The x-axis represents negative log2-transformed p-Values, and bars are colored by gene ontology category. (B) Chord diagram illustrating the relationships between representative genes and their associated biological processes.

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    Figure 4.

    Stage-specific survival analysis and prediction distributions. (A-C) Kaplan-Meier survival curves stratified by model predictions (Negative: predicted responders, Positive: predicted non-responders) across different disease stages: (A) Stage I/II patients showing significant survival difference (p=0.019); (B) Stage III patients showing no significant difference in survival outcomes (p=0.69); (C) Stage IV patients showing a non-significant trend toward better survival in predicted responders (p=0.2). Numbers of patients at risk are shown below each graph. (D) Box plot showing the distribution of prediction values across disease stages, with individual data points, medians (blue lines), and means (red dots) displayed. Higher prediction values indicate greater likelihood of non-response to chemotherapy.

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Cancer Genomics - Proteomics: 23 (3)
Cancer Genomics & Proteomics
Vol. 23, Issue 3
May-June 2026
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Transcriptome-based Deep Learning Model for Predicting Gemcitabine and Cisplatin Chemotherapy Response in Urothelial Carcinoma: Development and External Validation
JUWON KANG, HYUN JUNG LEE, SANG-BO OH, JONG KIL NAM, TAE UN KIM, HWASEONG RYU, YONG KAN KI, JIHOON KANG, YI RANG KIM, JEONG HOON LEE, JUNJEONG CHOI, YUN JEONG HONG, KWONOH PARK
Cancer Genomics & Proteomics May 2026, 23 (3) 546-557; DOI: 10.21873/cgp.20589

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Transcriptome-based Deep Learning Model for Predicting Gemcitabine and Cisplatin Chemotherapy Response in Urothelial Carcinoma: Development and External Validation
JUWON KANG, HYUN JUNG LEE, SANG-BO OH, JONG KIL NAM, TAE UN KIM, HWASEONG RYU, YONG KAN KI, JIHOON KANG, YI RANG KIM, JEONG HOON LEE, JUNJEONG CHOI, YUN JEONG HONG, KWONOH PARK
Cancer Genomics & Proteomics May 2026, 23 (3) 546-557; DOI: 10.21873/cgp.20589
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Keywords

  • Urothelial carcinoma
  • cisplatin
  • gemcitabine
  • chemotherapy response
  • deep learning
  • RNA sequencing
  • precision oncology
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