Use of patient‐derived tumor organoid platform to predict the benefit of postoperative adjuvant chemotherapy for poor responders to neoadjuvant chemoradiotherapy in locally advanced rectal cancer
Abstract Postoperative adjuvant chemotherapy (AC) for poor responders to neoadjuvant chemoradiotherapy (nCRT) remains debatable among patients with locally advanced rectal cancer (LARC), necessitating biomarkers to accurately predict the benefits of AC. This study aimed to develop a patient‐derived...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-11-01
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| Series: | Bioengineering & Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/btm2.10586 |
| _version_ | 1797556867847684096 |
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| author | Weisong Xue Ting Wang Jiaxin Yao Wei Wu Dexin Chen Botao Yan Xiaoyu Dong Yuting Tang Yunli Zeng Yueyu He Peihua Cao Fangyuan Shao Wenhua Huang Chuxia Deng Jun Yan |
| author_facet | Weisong Xue Ting Wang Jiaxin Yao Wei Wu Dexin Chen Botao Yan Xiaoyu Dong Yuting Tang Yunli Zeng Yueyu He Peihua Cao Fangyuan Shao Wenhua Huang Chuxia Deng Jun Yan |
| author_sort | Weisong Xue |
| collection | DOAJ |
| description | Abstract Postoperative adjuvant chemotherapy (AC) for poor responders to neoadjuvant chemoradiotherapy (nCRT) remains debatable among patients with locally advanced rectal cancer (LARC), necessitating biomarkers to accurately predict the benefits of AC. This study aimed to develop a patient‐derived tumor organoid (PDTO) platform to predict the benefit of AC in LARC patients showing poor nCRT response. PDTOs were established using irradiated rectal cancer specimens with poor nCRT responses, and their sensitivity to chemotherapy regimens was tested. The half‐maximal inhibitory concentration (IC50) value for the PDTO drug test was defined based on the clinical outcomes, and the accuracy of the PDTO prognostic predictions was calculated. Predictive models were developed and validated using the PDTO drug test results. Between October 2018 and December 2021, 86 PDTOs were successfully constructed from 138 specimens (success rate 62.3%). The optimal IC50 cut‐off value for the organoid drug test was 39.31 μmol/L, with a sensitivity of 84.75%, a specificity of 85.19%, and an accuracy of 84.88%. Multivariate Cox regression analysis revealed that the PDTO drug test was an independent predictor of prognosis. A nomogram based on the PDTO drug test was developed, showing good prognostic ability in predicting the 2‐year and 3‐year disease‐free survivals (AUC of 0.826 [95% CI, 0.721–0.931] and 0.902 [95% CI, 0.823–0.982], respectively) and overall survivals (AUC of 0.859 [95% CI, 0.745–0.973] and 0.885 [95% CI, 0.792–0.978], respectively). The PDTO drug test can predict the benefit of postoperative AC in poor responders with LARC to nCRT. |
| first_indexed | 2024-03-10T17:09:02Z |
| format | Article |
| id | doaj.art-a320570d70204bfea3f02464dfb91c08 |
| institution | Directory Open Access Journal |
| issn | 2380-6761 |
| language | English |
| last_indexed | 2024-03-10T17:09:02Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj.art-a320570d70204bfea3f02464dfb91c082023-11-20T10:44:12ZengWileyBioengineering & Translational Medicine2380-67612023-11-0186n/an/a10.1002/btm2.10586Use of patient‐derived tumor organoid platform to predict the benefit of postoperative adjuvant chemotherapy for poor responders to neoadjuvant chemoradiotherapy in locally advanced rectal cancerWeisong Xue0Ting Wang1Jiaxin Yao2Wei Wu3Dexin Chen4Botao Yan5Xiaoyu Dong6Yuting Tang7Yunli Zeng8Yueyu He9Peihua Cao10Fangyuan Shao11Wenhua Huang12Chuxia Deng13Jun Yan14Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University Guangzhou Guangdong People's Republic of ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University Guangzhou Guangdong People's Republic of ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University Guangzhou Guangdong People's Republic of ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University Guangzhou Guangdong People's Republic of ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University Guangzhou Guangdong People's Republic of ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University Guangzhou Guangdong People's Republic of ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University Guangzhou Guangdong People's Republic of ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University Guangzhou Guangdong People's Republic of ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University Guangzhou Guangdong People's Republic of ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University Guangzhou Guangdong People's Republic of ChinaClinical Research Center, Zhujiang Hospital, Department of Biostatistics School of Public Health, Southern Medical University Guangzhou Guangdong People's Republic of ChinaCancer Center, Faculty of Health Sciences University of Macau Macau People's Republic of ChinaGuangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy School of Basic Medical Sciences, Southern Medical University Guangzhou Guangdong People's Republic of ChinaCancer Center, Faculty of Health Sciences University of Macau Macau People's Republic of ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University Guangzhou Guangdong People's Republic of ChinaAbstract Postoperative adjuvant chemotherapy (AC) for poor responders to neoadjuvant chemoradiotherapy (nCRT) remains debatable among patients with locally advanced rectal cancer (LARC), necessitating biomarkers to accurately predict the benefits of AC. This study aimed to develop a patient‐derived tumor organoid (PDTO) platform to predict the benefit of AC in LARC patients showing poor nCRT response. PDTOs were established using irradiated rectal cancer specimens with poor nCRT responses, and their sensitivity to chemotherapy regimens was tested. The half‐maximal inhibitory concentration (IC50) value for the PDTO drug test was defined based on the clinical outcomes, and the accuracy of the PDTO prognostic predictions was calculated. Predictive models were developed and validated using the PDTO drug test results. Between October 2018 and December 2021, 86 PDTOs were successfully constructed from 138 specimens (success rate 62.3%). The optimal IC50 cut‐off value for the organoid drug test was 39.31 μmol/L, with a sensitivity of 84.75%, a specificity of 85.19%, and an accuracy of 84.88%. Multivariate Cox regression analysis revealed that the PDTO drug test was an independent predictor of prognosis. A nomogram based on the PDTO drug test was developed, showing good prognostic ability in predicting the 2‐year and 3‐year disease‐free survivals (AUC of 0.826 [95% CI, 0.721–0.931] and 0.902 [95% CI, 0.823–0.982], respectively) and overall survivals (AUC of 0.859 [95% CI, 0.745–0.973] and 0.885 [95% CI, 0.792–0.978], respectively). The PDTO drug test can predict the benefit of postoperative AC in poor responders with LARC to nCRT.https://doi.org/10.1002/btm2.10586adjuvant chemotherapyneoadjuvant chemoradiotherapynomogramorganoidrectal cancer |
| spellingShingle | Weisong Xue Ting Wang Jiaxin Yao Wei Wu Dexin Chen Botao Yan Xiaoyu Dong Yuting Tang Yunli Zeng Yueyu He Peihua Cao Fangyuan Shao Wenhua Huang Chuxia Deng Jun Yan Use of patient‐derived tumor organoid platform to predict the benefit of postoperative adjuvant chemotherapy for poor responders to neoadjuvant chemoradiotherapy in locally advanced rectal cancer Bioengineering & Translational Medicine adjuvant chemotherapy neoadjuvant chemoradiotherapy nomogram organoid rectal cancer |
| title | Use of patient‐derived tumor organoid platform to predict the benefit of postoperative adjuvant chemotherapy for poor responders to neoadjuvant chemoradiotherapy in locally advanced rectal cancer |
| title_full | Use of patient‐derived tumor organoid platform to predict the benefit of postoperative adjuvant chemotherapy for poor responders to neoadjuvant chemoradiotherapy in locally advanced rectal cancer |
| title_fullStr | Use of patient‐derived tumor organoid platform to predict the benefit of postoperative adjuvant chemotherapy for poor responders to neoadjuvant chemoradiotherapy in locally advanced rectal cancer |
| title_full_unstemmed | Use of patient‐derived tumor organoid platform to predict the benefit of postoperative adjuvant chemotherapy for poor responders to neoadjuvant chemoradiotherapy in locally advanced rectal cancer |
| title_short | Use of patient‐derived tumor organoid platform to predict the benefit of postoperative adjuvant chemotherapy for poor responders to neoadjuvant chemoradiotherapy in locally advanced rectal cancer |
| title_sort | use of patient derived tumor organoid platform to predict the benefit of postoperative adjuvant chemotherapy for poor responders to neoadjuvant chemoradiotherapy in locally advanced rectal cancer |
| topic | adjuvant chemotherapy neoadjuvant chemoradiotherapy nomogram organoid rectal cancer |
| url | https://doi.org/10.1002/btm2.10586 |
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