Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer
The efficacy of chemotherapy varies significantly among patients with gastric cancer (GC), and there is currently no effective strategy to predict chemotherapeutic outcomes. In this study, we successfully establish 57 GC patient-derived organoids (PDOs) from 73 patients with GC (78%). These organoid...
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sg-ntu-dr.10356-1816012024-12-15T15:39:01Z Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer Zhao, Yi Li, Shangru Zhu, Lefan Huang, Mingle Xie, Yubin Song, Xinming Chen, Zhihui Lau, Harry Cheuk-Hay Sung, Joseph Jao Yiu Xu, Lixia Yu, Jun Li, Xiaoxing Lee Kong Chian School of Medicine (LKCMedicine) Medicine, Health and Life Sciences Chemotherapy Gastric cancer The efficacy of chemotherapy varies significantly among patients with gastric cancer (GC), and there is currently no effective strategy to predict chemotherapeutic outcomes. In this study, we successfully establish 57 GC patient-derived organoids (PDOs) from 73 patients with GC (78%). These organoids retain histological characteristics of their corresponding primary GC tissues. GC PDOs show varied responses to different chemotherapeutics. Through RNA sequencing, the upregulation of tumor suppression genes/pathways is identified in 5-fluorouracil (FU)- or oxaliplatin-sensitive organoids, whereas genes/pathways associated with proliferation and invasion are enriched in chemotherapy-resistant organoids. Gene expression biomarker panels, which could distinguish sensitive and resistant patients to 5-FU and oxaliplatin (area under the dose-response curve [AUC] >0.8), are identified. Moreover, the drug-response results in PDOs are validated in patient-derived organoids-based xenograft (PDOX) mice and are consistent with the actual clinical response in 91.7% (11/12) of patients with GC. Assessing chemosensitivity in PDOs can be utilized as a valuable tool for screening chemotherapeutic drugs in patients with GC. Published version This work was supported by the National Natural Science Foundation of China (82173191), the Guangdong Basic and Applied Basic Research Foundation (2019B151502009), and Kelin Outstanding Young Scientist of the First Affiliated Hospital of Sun Yat-sen University (Y12002). 2024-12-10T06:29:37Z 2024-12-10T06:29:37Z 2024 Journal Article Zhao, Y., Li, S., Zhu, L., Huang, M., Xie, Y., Song, X., Chen, Z., Lau, H. C., Sung, J. J. Y., Xu, L., Yu, J. & Li, X. (2024). Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer. Cell Reports Medicine, 5(7), 101627-. https://dx.doi.org/10.1016/j.xcrm.2024.101627 2666-3791 https://hdl.handle.net/10356/181601 10.1016/j.xcrm.2024.101627 38964315 2-s2.0-85198266808 7 5 101627 en Cell Reports Medicine © 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). application/pdf |
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Medicine, Health and Life Sciences Chemotherapy Gastric cancer Zhao, Yi Li, Shangru Zhu, Lefan Huang, Mingle Xie, Yubin Song, Xinming Chen, Zhihui Lau, Harry Cheuk-Hay Sung, Joseph Jao Yiu Xu, Lixia Yu, Jun Li, Xiaoxing Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer |
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The efficacy of chemotherapy varies significantly among patients with gastric cancer (GC), and there is currently no effective strategy to predict chemotherapeutic outcomes. In this study, we successfully establish 57 GC patient-derived organoids (PDOs) from 73 patients with GC (78%). These organoids retain histological characteristics of their corresponding primary GC tissues. GC PDOs show varied responses to different chemotherapeutics. Through RNA sequencing, the upregulation of tumor suppression genes/pathways is identified in 5-fluorouracil (FU)- or oxaliplatin-sensitive organoids, whereas genes/pathways associated with proliferation and invasion are enriched in chemotherapy-resistant organoids. Gene expression biomarker panels, which could distinguish sensitive and resistant patients to 5-FU and oxaliplatin (area under the dose-response curve [AUC] >0.8), are identified. Moreover, the drug-response results in PDOs are validated in patient-derived organoids-based xenograft (PDOX) mice and are consistent with the actual clinical response in 91.7% (11/12) of patients with GC. Assessing chemosensitivity in PDOs can be utilized as a valuable tool for screening chemotherapeutic drugs in patients with GC. |
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Lee Kong Chian School of Medicine (LKCMedicine) |
author_facet |
Lee Kong Chian School of Medicine (LKCMedicine) Zhao, Yi Li, Shangru Zhu, Lefan Huang, Mingle Xie, Yubin Song, Xinming Chen, Zhihui Lau, Harry Cheuk-Hay Sung, Joseph Jao Yiu Xu, Lixia Yu, Jun Li, Xiaoxing |
format |
Article |
author |
Zhao, Yi Li, Shangru Zhu, Lefan Huang, Mingle Xie, Yubin Song, Xinming Chen, Zhihui Lau, Harry Cheuk-Hay Sung, Joseph Jao Yiu Xu, Lixia Yu, Jun Li, Xiaoxing |
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Zhao, Yi |
title |
Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer |
title_short |
Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer |
title_full |
Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer |
title_fullStr |
Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer |
title_full_unstemmed |
Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer |
title_sort |
personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer |
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2024 |
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https://hdl.handle.net/10356/181601 |
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1819113010676891648 |