Single-cell RNA sequencing via endoscopic ultrasound-guided fine-needle biopsy for pancreatic tumors uncovered an aggressive subclone with a poor prognosis
Background: Single-cell RNA sequencing (scRNA-seq) is a powerful tool which can unveil regulatory connections between genes and cells. However, due to the high demand for tissue quality, most scRNA-seq for pancreatic cancer is carried out by surgical specimen. This study (NCT05767697) aims to gain p...
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Elsevier
2025-03-01
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| Series: | ESMO Gastrointestinal Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2949819824000748 |
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| author | Y.-Y. Su M.-Y. Lin S.M. Cheng W.-L. Chang C.-W. Hsu C.-M. Yeh C.-C. Yu Y.-C. Hou C.-J. Huang Y.-S. Liu Y.-J. Chao D.-Y. Hwang Y.S. Shan L.-T. Chen |
| author_facet | Y.-Y. Su M.-Y. Lin S.M. Cheng W.-L. Chang C.-W. Hsu C.-M. Yeh C.-C. Yu Y.-C. Hou C.-J. Huang Y.-S. Liu Y.-J. Chao D.-Y. Hwang Y.S. Shan L.-T. Chen |
| author_sort | Y.-Y. Su |
| collection | DOAJ |
| description | Background: Single-cell RNA sequencing (scRNA-seq) is a powerful tool which can unveil regulatory connections between genes and cells. However, due to the high demand for tissue quality, most scRNA-seq for pancreatic cancer is carried out by surgical specimen. This study (NCT05767697) aims to gain practical experience in carrying out scRNA-seq using endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). Materials and methods: With a within-subjects design, two punctures from the same lesion, with a negative pressure of 5 ml (suction group) and without applying suction (non-suction group), were evaluated. Each biopsy sample was separated into three parts: white tissue, red material, and buffer for living cell counting. scRNA-seq was carried out according to the manufacturer’s protocol. The pancreatic adenocarcinoma dataset in The Cancer Genome Atlas (TCGA) was used as external validation. Results: A total of 20 patients with 40 specimens were enrolled. The suction group achieved a success rate of 80% (16/20), which was significantly higher than the 10% (2/20) success rate in the non-suction group (P < 0.001). scRNA-seq data were generated for four patients, including two early stage and two late stage. Overall, 15 major cell subtypes, including 4 cancer subclones, were identified across early and late stages. Analysis of differentially expressed genes identified an aggressive subclone highlighted by ubiquitin-conjugating enzyme E2 C (UBE2C) high expression, commonly in late stage. The TCGA dataset also demonstrated that UBE2C high-expression pancreatic cancer had a poor prognosis. Conclusions: EUS-FNB with a negative pressure of 5 ml is feasible for scRNA-seq in clinical practice. A UBE2C high-expression subclone correlates with a poor prognosis, potentially becoming a new therapeutic target in future studies. |
| format | Article |
| id | doaj-art-afb799154dfa421691c55347f0103357 |
| institution | Kabale University |
| issn | 2949-8198 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
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| series | ESMO Gastrointestinal Oncology |
| spelling | doaj-art-afb799154dfa421691c55347f01033572025-08-20T03:42:37ZengElsevierESMO Gastrointestinal Oncology2949-81982025-03-01710011310.1016/j.esmogo.2024.100113Single-cell RNA sequencing via endoscopic ultrasound-guided fine-needle biopsy for pancreatic tumors uncovered an aggressive subclone with a poor prognosisY.-Y. Su0M.-Y. Lin1S.M. Cheng2W.-L. Chang3C.-W. Hsu4C.-M. Yeh5C.-C. Yu6Y.-C. Hou7C.-J. Huang8Y.-S. Liu9Y.-J. Chao10D.-Y. Hwang11Y.S. Shan12L.-T. Chen13National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Tainan, TaiwanDepartment of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Tainan, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Tainan, TaiwanCollege of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Diagnostic Radiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, TainanDepartment of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Biomarkers and Biotech Drugs, Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; Dr Daw-Yang Hwang, National Health Research Institutes, No. 367, Sheng-Li Road, Tainan 70428, Taiwan. Tel: +886-6-7000123 Ext: 65163Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Dr Yan-Shen Shan, National Cheng Kung University, College of Medicine, 138, Sheng-Li Road, Tainan 70428, Taiwan. Tel: +886-6-2353535 Ext: 5182; Fax: +886-6-2766676National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Correspondence to: Dr Li-Tzong Chen, Kaohsiung Medical University Hospital, 100, Tzyou 1st Road, Kaohsiung City 80756, Taiwan. Tel: +886-7-3121101 Ext: 7451; Fax: +886-7-3135612Background: Single-cell RNA sequencing (scRNA-seq) is a powerful tool which can unveil regulatory connections between genes and cells. However, due to the high demand for tissue quality, most scRNA-seq for pancreatic cancer is carried out by surgical specimen. This study (NCT05767697) aims to gain practical experience in carrying out scRNA-seq using endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). Materials and methods: With a within-subjects design, two punctures from the same lesion, with a negative pressure of 5 ml (suction group) and without applying suction (non-suction group), were evaluated. Each biopsy sample was separated into three parts: white tissue, red material, and buffer for living cell counting. scRNA-seq was carried out according to the manufacturer’s protocol. The pancreatic adenocarcinoma dataset in The Cancer Genome Atlas (TCGA) was used as external validation. Results: A total of 20 patients with 40 specimens were enrolled. The suction group achieved a success rate of 80% (16/20), which was significantly higher than the 10% (2/20) success rate in the non-suction group (P < 0.001). scRNA-seq data were generated for four patients, including two early stage and two late stage. Overall, 15 major cell subtypes, including 4 cancer subclones, were identified across early and late stages. Analysis of differentially expressed genes identified an aggressive subclone highlighted by ubiquitin-conjugating enzyme E2 C (UBE2C) high expression, commonly in late stage. The TCGA dataset also demonstrated that UBE2C high-expression pancreatic cancer had a poor prognosis. Conclusions: EUS-FNB with a negative pressure of 5 ml is feasible for scRNA-seq in clinical practice. A UBE2C high-expression subclone correlates with a poor prognosis, potentially becoming a new therapeutic target in future studies.http://www.sciencedirect.com/science/article/pii/S2949819824000748pancreatic cancertranscriptome analysistumor heterogeneityUBE2C |
| spellingShingle | Y.-Y. Su M.-Y. Lin S.M. Cheng W.-L. Chang C.-W. Hsu C.-M. Yeh C.-C. Yu Y.-C. Hou C.-J. Huang Y.-S. Liu Y.-J. Chao D.-Y. Hwang Y.S. Shan L.-T. Chen Single-cell RNA sequencing via endoscopic ultrasound-guided fine-needle biopsy for pancreatic tumors uncovered an aggressive subclone with a poor prognosis ESMO Gastrointestinal Oncology pancreatic cancer transcriptome analysis tumor heterogeneity UBE2C |
| title | Single-cell RNA sequencing via endoscopic ultrasound-guided fine-needle biopsy for pancreatic tumors uncovered an aggressive subclone with a poor prognosis |
| title_full | Single-cell RNA sequencing via endoscopic ultrasound-guided fine-needle biopsy for pancreatic tumors uncovered an aggressive subclone with a poor prognosis |
| title_fullStr | Single-cell RNA sequencing via endoscopic ultrasound-guided fine-needle biopsy for pancreatic tumors uncovered an aggressive subclone with a poor prognosis |
| title_full_unstemmed | Single-cell RNA sequencing via endoscopic ultrasound-guided fine-needle biopsy for pancreatic tumors uncovered an aggressive subclone with a poor prognosis |
| title_short | Single-cell RNA sequencing via endoscopic ultrasound-guided fine-needle biopsy for pancreatic tumors uncovered an aggressive subclone with a poor prognosis |
| title_sort | single cell rna sequencing via endoscopic ultrasound guided fine needle biopsy for pancreatic tumors uncovered an aggressive subclone with a poor prognosis |
| topic | pancreatic cancer transcriptome analysis tumor heterogeneity UBE2C |
| url | http://www.sciencedirect.com/science/article/pii/S2949819824000748 |
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