Identification of cancer-related genes FGFR2 and CEBPB in choledochal cyst via RNA sequencing of patient-derived liver organoids

Q: What was the main objective of the study on choledochal cysts?

To identify gene expression changes and dysregulated cancer-related genes that may explain the cancer risk in CC patients.

Q: How were liver organoids and gene expression profiles generated?

Liver organoids (n = 51) were produced from CC and hepatoblastoma biopsy samples, followed by RNA sequencing and bioinformatics to detect differentially expressed genes.

Q: Which genes showed elevated expression in CC tissues and were validated?

FGFR2 and CEBPB were significantly elevated in CC liver tissues, with validation by RT-qPCR and immunohistochemistry showing positive staining in bile ducts.

Sep 24, 2026

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Study examines how choledochal cysts (CC), congenital bile duct anomalies with 6–30% bile duct cancer risk, develop cancer at a molecular level. RNA sequencing of liver organoids generated from CC, hepatoblastoma non-tumor, and hepatoblastoma tumor tissues was used to discover cancer-related expression changes. Bioinformatics identified dysregulated genes, then RT-qPCR and immunohistochemistry validated FGFR2 and CEBPB elevation, implicating these pathways in CC cancer development.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Abstract

Background

Methods

Findings

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Introduction

PLOS ONE OPEN ACCESS Citation: Ye Y, Lui VCH, Babu RO, Wu Z, Wu W, Chung PHY, et al. (2023) Identification of cancerrelated genes FGFR2 and CEBPB in choledochal cyst via RNA sequencing of patient-derived liver organoids. PLoS ONE 18(3): e0283737 . [https://doi](https://doi). org/10 .1371/journal.pone.0283737 Editor: Gianfranco D. Alpini, Texas A&M University, UNITED STATES Received: January 12, 2023 Accepted: March 15, 2023 Published: March 30, 2023 Copyright: © 2023 Ye et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files. Funding: The author(s) received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Abbreviations: CC, Choledochal cyst; HB, hepatoblastoma; FGFR2, fibroblast growth factor RESEARCH ARTICLE Identification of cancer-related genes FGFR2 and CEBPB in choledochal cyst via RNA sequencing of patient-derived liver organoids Yongqin Ye1,2,3☯, Vincent Chi Hang Lui1,4☯, Rosana Ottakandathil Babu1☯¤, Zhongluan Wu1, Weifang Wu3, Patrick Ho Yu Chung1,5, Kenneth KakYuen Wong1,5, Bin Wang3 *, Paul Kwong Hang Tam1,2,4,5 * 1 Department of Surgery, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China, 2 Faculty of Medicine, Macau University of Science and Technology, Macau SAR, China, 3 Department of General Surgery, Shenzhen Children’s Hospital, Shenzhen, Guangdong, China, 4 Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong, China, 5 Department of Surgery, University of Hong KongShenzhen Hospital, Shenzhen, Guangdong, China ☯ These authors contributed equally to this work. ¤ Current address: MRC WIMM Centre For Computational Biology, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom * [szwb1967@126.com](szwb1967@126.com) (BW); [pkhtam@must.edu.mo](pkhtam@must.edu.mo) (PKHT) Abstract Background Choledochal cysts (CC) are congenital bile duct anomalies with 6–30% risk for developing bile duct cancer. However, the molecular mechanisms underlying cancer risk of CC are unknown. We sought to identify the gene expression changes underlying the cancer risk of CC patients. Methods Liver organoids (n = 51) were generated from liver/bile duct biopsies of CC (n = 7; type I) and hepatoblastoma (n = 5; HB: non-tumor & tumor) for RNA sequencing. Bioinformatics analysis was conducted to identify differentially expressed cancer-related genes in CC and controls. We compared CC with non-cancerous and cancerous controls, normal adjacent non-tumor region of hepatoblastoma (HB) liver as non-cancerous control and tumor region as non-CC cancer control (HB-tumor) . Reverse transcription real-time quantitative PCR (RT-qPCR) verification and immunohistochemistry of selected genes was conducted in additional CC and HB liver biopsies. Findings HB non-tumor and HB tumor organoids displayed distinct gene expression profiles. Expression profiling separated CC organoids into two clusters, one overlapping with HB non-tumor and the other one with HB tumor organoids. Genes selected based on their log2FoldChange values for RT-qPCR verification in 31 CC and 11 HB non-tumor liver tissues revealed significantly elevated expression of FGFR2 in 7 and CEBPB in 2 CC liver tissues (CC vs HB: receptor 2; CEBPB, CCAAT/enhancer-binding protein beta; RNAseq, RNA sequencing. 4.082 vs. 0.7671, p<0.01; 2.506 vs. 1.210, p<0.01) . Distinctive positive staining in bile ducts were seen in CC, HB tumor and non-tumor liver tissues for FGFR2 and CEBPB. Percentages of CEBPB-immuno-positive or FGFR2-immuno-positive bile duct ce

FAQs

What was the main objective of the study on choledochal cysts?

To identify gene expression changes and dysregulated cancer-related genes that may explain the cancer risk in CC patients.

How were liver organoids and gene expression profiles generated?

Liver organoids (n = 51) were produced from CC and hepatoblastoma biopsy samples, followed by RNA sequencing and bioinformatics to detect differentially expressed genes.

Which genes showed elevated expression in CC tissues and were validated?

FGFR2 and CEBPB were significantly elevated in CC liver tissues, with validation by RT-qPCR and immunohistochemistry showing positive staining in bile ducts.

Sep 24, 2026

Uploaded by Logic