Evidence map›Paper›PMID 40741875›Full record

ArticleClinical and translational medicine2025

Analysis of hepatitis B virus integration identifies KMT2B as a novel cancer-related gene in pancreatic cancer.

Mengge Li, Huimin Li, Dejun Liu, Shunan Liu, Hui Yuan, Yan Wu, Min Du, Yuan Fang, Jin Li, Hui Cong and 7 more

Abstract read
In one paragraph

Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Mengge LiState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Huimin LiState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Dejun LiuDepartment of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID 0000-0002-8091-0375
Shunan LiuState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hui YuanState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yan WuState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Min DuState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuan FangOrgan Transplantation Center, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Jin LiState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hui CongState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Dan ZhaoState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chunsun FanState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Qing WangState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cenkai ShenShanghai Medical College, Fudan University, Shanghai, China.
Yu GanState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID 0000-0002-5769-6809
Yongwei SunDepartment of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hong TuState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID 0000-0002-8298-5207

Funding

Chinese State Key Laboratory of Oncogenes and Related Genes ZZ91-1416Chinese State Key Laboratory of Oncogenes and Related Genes ZZ91-1506Chinese State Key Laboratory of Oncogenes and Related Genes ZZ94-2109National Key Projects Specialized in Infectious Diseases 2017ZX10201201-008-003National Key R&D Program of China 2017YFC0908103National Key R&D Program of China 2017YFC0908104National Natural Science Foundation of China 81572312National Natural Science Foundation of China 82203225National Undergraduate Innovation and Entrepreneurship Training Program/FDUROP (Wangdao project) 202010246037/19058Natural Science Foundation of Shanghai 24ZR1465400
6 · The paper itself

Abstract

backgroundPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with few well-established risk factors. Emerging epidemiological evidence suggests a link between hepatitis B virus (HBV) infection and PDAC. However, the underlying mechanisms remain unclear.

methodsHigh-throughput sequencing-based approach was employed to identify HBV integrations in tumour and para-tumour tissues of PDAC. The biological functions of KMT2B were evaluated in PDAC cell lines as well as in subcutaneous and orthotopic mouse models of PDAC. Chromatin immunoprecipitation sequencing and RNA sequencing were used to identify the pathway involved in PDAC development.

resultsHBV integration was detected in approximately one-third of HBV DNA-positive PDAC and adjacent para-tumour tissues. A total of 425 viral‒host junctions were identified, with the majority located in intergenic regions (51.29%), followed by introns (43.29%) and exons (2.35%) of the human genome. Lysine methyltransferase 2B (KMT2B, also known as MLL4), a gene frequently targeted by HBV integration in hepatocellular carcinoma, was also found to be interrupted by HBV in PDAC. KMT2B was significantly upregulated in PDAC and promoted malignant behaviours both in vitro and in vivo. Mechanistically, KMT2B exerts its oncogenic effects by regulating the downstream target gene FYN through histone H3K4 trimethylation, leading to the activation of the PI3K/Akt signalling pathway.

conclusionHBV integration is a common event in HBV-related PDAC and KMT2B has been identified as a novel PDAC-related gene. KEY POINTS: Hepatitis B virus (HBV) integrates in both tumour and adjacent para-tumour tissues of pancreatic ductal adenocarcinoma (PDAC). KMT2B, a target gene of HBV integration, promotes PDAC proliferation and metastasis in vivo and in vitro experiments. KMT2B exerts its oncogenic effects by regulating the downstream target gene FYN via histone H3K4 trimethylation, activating the PI3K/Akt signalling pathway.

Indexed as

Carcinoma, Pancreatic DuctalDNA-Binding ProteinsHepatitis B virusHistone-Lysine N-MethyltransferasePancreatic NeoplasmsVirus IntegrationAnimalsCell Line, TumorFemaleHepatitis BHumansMaleMiceDNA-Binding ProteinsHistone-Lysine N-MethyltransferaseMLL4 protein, humanFYNhepatitis B virusintegrationKMT2Bpancreatic ductal adenocarcinoma

Identifiers

PMID40741875
PMCPMC12311841

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.