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

Xue, Weisong1,2,3; Wang, Ting1; Yao, Jiaxin1; Wu, Wei1; Chen, Dexin1; Yan, Botao1; Dong, Xiaoyu1; Tang, Yuting1; Zeng, Yunli1; He, Yueyu1; Cao, Peihua4; Shao, Fangyuan5; Huang, Wenhua6,9; Deng, Chuxia8; Yan, Jun1,7

2023-08-01

10.1002/btm2.10586

BIOENGINEERING & TRANSLATIONAL MEDICINE   Impact Factor & Quartile

2380-6761

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 mu mol/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.

adjuvant chemotherapy neoadjuvant chemoradiotherapy nomogram organoid rectal cancer

SCI

English

Others

National Natural Science Foundation of China["82273360","31972915","32271181"] ; National Key Ramp;D Program of China[2022YFB4600600] ; Guangdong Provincial Major Talents Project[2019JC05Y361] ; Fu Jian Medical Innovation Project[2022CXA028] ; Science and Technology Planning Project of Guangzhou City[202206010085] ; China Postdoctoral Science Foundation[2020 M682789] ; Clinical Research Project of Nanfang Hospital["2018CR034","2020CR001","2020CR011"] ; President Foundation of Nanfang Hospital, Southern Medical University[2019Z023] ; Training Program for Undergraduate Innovation and Entrepreneurship["202212121011","S202212121092","S202212121104"] ; Guangdong Basic and Applied Basic Research Foundation[2020B1515120001]

Biotechnology & Applied Microbiology ; Engineering ; Pharmacology & Pharmacy

Biotechnology & Applied Microbiology ; Engineering, Biomedical ; Pharmacology & Pharmacy

WOS:001049903700001

WILEY

Web of Science

1.Southern Med Univ, Nanfang Hosp, Sch Clin Med 1, Dept Gen Surg,Guangdong Provincial Key Lab Precis, Guangzhou, Guangdong, Peoples R China
2.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Gastrointestinal Surg, Shenzhen, Guangdong, Peoples R China
3.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Dept Gastrointestinal Surg, Shenzhen, Guangdong, Peoples R China
4.Southern Med Univ, Zhujiang Hosp, Clin Res Ctr, Sch Publ Hlth, Guangzhou, Guangdong, Peoples R China
5.Univ Macau, Fac Hlth Sci, Canc Ctr, Macau, Peoples R China
6.Southern Med Univ, Guangdong Engn Res Ctr Translat Med Printing Appli, Sch Basic Med Sci, Guangdong Prov Key Lab Digital Med & Biomech,Natl, Guangzhou, Guangdong, Peoples R China
7.Southern Med Univ, Nanfang Hosp, Dept Gen Surg, Guangzhou 510515, Guangdong, Peoples R China
8.Univ Macau, Fac Hlth Sci, Canc Ctr, Macau, Peoples R China
9.Southern Med Univ, Sch Basic Med Sci, PeoplesRepubl China, Guangzhou 510515, Guangdong, Peoples R China

Xue, Weisong,Wang, Ting,Yao, Jiaxin,et al. 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[J]. BIOENGINEERING & TRANSLATIONAL MEDICINE,2023.

Xue, Weisong.,Wang, Ting.,Yao, Jiaxin.,Wu, Wei.,Chen, Dexin.,...&Yan, Jun.(2023).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.

Xue, Weisong,et al."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 (2023).