PBRM1 presents a potential prognostic marker and therapeutic target in duodenal papillary carcinoma Article Swipe
Xujun He
,
Ji Xu
,
Nan Niu
,
Guoxi Xu
,
Honglin Zhu
,
Zhengchuang Liu
,
Yiping Mou
,
Zhengyuan Qian
,
Hui‐Ju Wang
,
Junfeng Hu
,
Tonghui Ma
,
Jie Ma
,
Hou‐Quan Tao
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1002/ctm2.1062
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1002/ctm2.1062
Background Due to its rarity, duodenal papillary carcinoma (DPC) is seldom studied as a unique disease and no specific molecular features or treatment guidelines are provided. Methods Whole‐exome sequencing was performed to gain new insights into the DPC mutation landscape and to identify potential signalling pathways and therapeutic targets. Mechanistically, immunohistochemistry (IHC), immunofluorescence, RNA‐seq, ATAC‐seq and in vitro cell function experiments were performed to confirm the underlying mechanisms. Results We described the mutational landscape of DPC for the first time as a group of rare tumours with a high frequency of dysregulation in the chromatin remodelling pathway, particularly PBRM1‐inactivating mutations that are significantly higher than duodenal adenocarcinomas and ampullary adenocarcinoma (27% vs. 0% vs. 7%, p < .01 ). In vitro cell experiments showed that downregulation of PBRM1 expression could significantly promote the cancer progression and epithelial‐to‐mesenchymal transition via the PBRM1‐c‐JUN‐VIM axis. The IHC data indicated that PBRM1 deficiency ( p = .047 ) and c‐JUN expression ( p < .001 ) were significantly associated with poor prognosis. Meanwhile, the downregulation of PBRM1 expression in HUTU‐80 cells was sensitive to radiation, which may be due to the suppression of c‐JUN by irradiation. Conclusions Our findings define a novel molecular subgroup of PBRM1‐inactivating mutations in DPC. PBRM1 play an important role in DPC progression and may serve as a potential therapeutic target and prognostic indicator.
Related Topics
Concepts
Downregulation and upregulation
Cancer research
Epithelial–mesenchymal transition
Immunohistochemistry
Exome sequencing
Medicine
Mutation
Biology
Internal medicine
Gene
Genetics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/ctm2.1062
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.1062
- OA Status
- gold
- Cited By
- 2
- References
- 47
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4298088086
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4298088086Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1002/ctm2.1062Digital Object Identifier
- Title
-
PBRM1 presents a potential prognostic marker and therapeutic target in duodenal papillary carcinomaWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-09-30Full publication date if available
- Authors
-
Xujun He, Ji Xu, Nan Niu, Guoxi Xu, Honglin Zhu, Zhengchuang Liu, Yiping Mou, Zhengyuan Qian, Hui‐Ju Wang, Junfeng Hu, Tonghui Ma, Jie Ma, Hou‐Quan TaoList of authors in order
- Landing page
-
https://doi.org/10.1002/ctm2.1062Publisher landing page
- PDF URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.1062Direct link to full text PDF
- Open access
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YesWhether a free full text is available
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-
goldOpen access status per OpenAlex
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.1062Direct OA link when available
- Concepts
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Downregulation and upregulation, Cancer research, Epithelial–mesenchymal transition, Immunohistochemistry, Exome sequencing, Medicine, Mutation, Biology, Internal medicine, Gene, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
2Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2Per-year citation counts (last 5 years)
- References (count)
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47Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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