Yang JL, Zhang JF, Gu JY, Gao M, Zheng MY, Guo SX, Zhang T. Strategic insights into the cultivation of pancreatic cancer organoids from endoscopic ultrasonography-guided biopsy tissue. World J Gastroenterol 2024; 30(42): 4532-4543 [PMID: 39563744 DOI: 10.3748/wjg.v30.i42.4532]
Corresponding Author of This Article
Tao Zhang, MM, Associate Professor, Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, No. 118 Xingguang Avenue, Liangjiang New Area, Chongqing 401147, China. tzhang04@126.com
Research Domain of This Article
Oncology
Article-Type of This Article
Prospective Study
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Yang JL, Zhang JF, Gu JY, Gao M, Zheng MY, Guo SX, Zhang T. Strategic insights into the cultivation of pancreatic cancer organoids from endoscopic ultrasonography-guided biopsy tissue. World J Gastroenterol 2024; 30(42): 4532-4543 [PMID: 39563744 DOI: 10.3748/wjg.v30.i42.4532]
World J Gastroenterol. Nov 14, 2024; 30(42): 4532-4543 Published online Nov 14, 2024. doi: 10.3748/wjg.v30.i42.4532
Strategic insights into the cultivation of pancreatic cancer organoids from endoscopic ultrasonography-guided biopsy tissue
Jia-Li Yang, Jun-Feng Zhang, Jian-You Gu, Mei Gao, Ming-You Zheng, Shi-Xiang Guo, Tao Zhang
Jia-Li Yang, Jun-Feng Zhang, Jian-You Gu, Mei Gao, Ming-You Zheng, Shi-Xiang Guo, Tao Zhang, Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
Co-first authors: Jia-Li Yang and Jun-Feng Zhang.
Co-corresponding authors: Shi-Xiang Guo and Tao Zhang.
Author contributions: Yang JL and Zhang JF designed study, conducted experiment, collected the data and wrote article; Gu JY contributed to the analysis; Gao M guided the cultivation technique; Zheng MY provided clinical advice; Guo SX and Zhang T operated endoscopes, collected samples and revised article.
Supported bythe Chongqing Talent Plan “Contract System” Project, No. cstc2022ycjh-bgzxm0137; and Natural Science Foundation of Chongqing, No. CSTB2024NSCQ-MSX0003.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Chongqing General Hospital. The ethics review number: No. KY S2022-045-01.
Clinical trial registration statement: The protocol registered at Chinese Clinical Trial Registry. The registration identification number: No. ChiCTR2200064388.
Informed consent statement: All participants or their legal guardian signed informed consent forms allowing their puncture samples and medical data to be used for scientific research.
Conflict-of-interest statement: The authors declare that there is no conflict of interest.
Data sharing statement: Datasets generated during the current study are available upon reasonable request.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Corresponding author: Tao Zhang, MM, Associate Professor, Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, No. 118 Xingguang Avenue, Liangjiang New Area, Chongqing 401147, China. tzhang04@126.com
Received: May 6, 2024 Revised: September 10, 2024 Accepted: October 16, 2024 Published online: November 14, 2024 Processing time: 178 Days and 8.3 Hours
Abstract
BACKGROUND
The frequent suboptimal efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) to culture pancreatic cancer (PC) organoids (PCOs) poses a major challenge in the advancement of personalized medicine for advanced PC.
AIM
To explore how to obtain appropriate puncture tissues from EUS-FNB and optimize the strategy for efficiently constructing PCOs, providing an efficient tool for the advancement of personalized medicine.
METHODS
Patients who underwent EUS-FNB for the diagnosis of PC tissue were prospectively enrolled. We refined the endoscopic biopsy procedures and organoid cultivation techniques. All tissue specimens verified by on-site pathological assessment were cultured in a semi-suspended medium in a microfluidic environment. We assessed differences in PCOs cultured beyond and below five generations examining patient demographics, specimen and organoid attributes, and the sensitivity of organoids to a panel of clinical drugs through cell viability assays.
RESULTS
In this study, 16 patients with PC were recruited, one sample was excluded because onsite cytopathology showed no tumor cells. Successful organoid generation occurred in 93.3% (14 of 15) of the EUS-FNB specimens, with 60% (9 of 15) sustaining over five generations. Among these patients, those with a history of diabetes, familial cancer, or larger tumors exhibited enhanced PCO expandability. The key factors influencing long-term PCOs expansion included initial needle sample quality (P = 0.005), rapid initiation of organoid culture post-isolation (P ≤ 0.001), and high organoid activity (P = 0.031). Drug sensitivity analysis revealed a partial response in two patients following therapeutic intervention and surgery and stable disease in four patients, indicating a moderate correlation between organoid response and clinical outcomes.
CONCLUSION
Optimal initial needle sampling, rapid and precise biopsy sample processing, process isolated samples as soon as possible, and sufficient cellular material are crucial for successful cultivating PCOs. High organoid activity is an important factor in maintaining their long-term expansion, which is essential for shortening the time of drug sensitivity analysis and is the basis of PC research.
Core Tip: We optimized the endoscopic ultrasound puncture process to obtain pancreatic cancer tissue and cultivate pancreatic cancer organoids. Adequate material from the first puncture, rapid and accurate puncture operations, and rapid entry of puncture samples into the culture stage are important factors for successfully cultivating pancreatic cancer organoids. Organoid activity is the key to long-term expansion.
