Single-cell RNA sequencing via endoscopic ultrasound-guided fine-needle biopsy for pancreatic tumors uncovered an aggressive subclone with a poor prognosis

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

ESMO Gastrointestinal Oncology (Mar 2025)

Single-cell RNA sequencing via endoscopic ultrasound-guided fine-needle biopsy for pancreatic tumors uncovered an aggressive subclone with a poor prognosis

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

Affiliations

Y.-Y. Su: National 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
M.-Y. Lin: Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
S.M. Cheng: National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
W.-L. Chang: Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
C.-W. Hsu: Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
C.-M. Yeh: National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
C.-C. Yu: National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
Y.-C. Hou: College of Medicine, National Cheng Kung University, Tainan, Taiwan
C.-J. Huang: Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Y.-S. Liu: Department of Diagnostic Radiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
Y.-J. Chao: Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
D.-Y. Hwang: National 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: 65163
Y.S. Shan: Department 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: +886-6-2766676
L.-T. Chen: National 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: +886-7-3135612

Journal volume & issue: Vol. 7
p. 100113

Abstract

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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.

Published in ESMO Gastrointestinal Oncology

ISSN: 2949-8198 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.sciencedirect.com/journal/esmo-gastrointestinal-oncology

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