Copy number loss of KDM5D may be a predictive biomarker for ATR inhibitor treatment in male patients with pulmonary squamous cell carcinoma
Article Swipe
Ayako Ura
,
Takuo Hayashi
,
Kazumasa Komura
,
Masaki Hosoya
,
Kazuya Takamochi
,
Eiichi Sato
,
Satomi Saito
,
Susumu Wakai
,
Takafumi Handa
,
Tsuyoshi Saito
,
Shunsuke Kato
,
Kenji Suzuki
,
Takashi Yao
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1002/cjp2.350
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1002/cjp2.350
A limited number of patients with lung squamous cell carcinoma (SCC) benefit clinically from molecular targeted drugs because of a lack of targetable driver alterations. We aimed to understand the prevalence and clinical significance of lysine‐specific demethylase 5D ( KDM5D ) copy number loss in SCC and explore its potential as a predictive biomarker for ataxia‐telangiectasia and Rad3‐related (ATR) inhibitor treatment. We evaluated KDM5D copy number loss in 173 surgically resected SCCs from male patients using fluorescence in situ hybridization. KDM5D copy number loss was detected in 75 of the 173 patients (43%). Genome‐wide expression profiles of the transcription start sites (TSSs) were obtained from 17 SCCs, for which the cap analysis of gene expression assay was performed, revealing that upregulated genes in tumors with the KDM5D copy number loss are associated with ‘cell cycle’, whereas downregulated genes in tumors with KDM5D copy number loss were associated with ‘immune response’. Clinicopathologically, SCCs with KDM5D copy number loss were associated with late pathological stage ( p = 0.0085) and high stromal content ( p = 0.0254). Multiplexed fluorescent immunohistochemistry showed that the number of tumor‐infiltrating CD8 + /T‐bet + T cells was lower in SCCs with KDM5D copy number loss than in wild‐type tumors. In conclusion, approximately 40% of the male patients with SCC exhibited KDM5D copy number loss. Tumors in patients who show this distinct phenotype can be ‘cold tumors’, which are characterized by the paucity of tumor T‐cell infiltration and usually do not respond to immunotherapy. Thus, they may be candidates for trials with ATR inhibitors.
Related Topics
Concepts
Copy-number variation
Cancer research
Biomarker
Gene dosage
Immunohistochemistry
Pathology
Biology
Fluorescence in situ hybridization
Medicine
Gene expression
Gene
Chromosome
Genome
Biochemistry
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/cjp2.350
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cjp2.350
- OA Status
- gold
- Cited By
- 1
- References
- 43
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4388768494
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4388768494Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1002/cjp2.350Digital Object Identifier
- Title
-
Copy number loss of KDM5D may be a predictive biomarker for
ATR inhibitor treatment in male patients with pulmonary squamous cell carcinomaWork title - Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-11-16Full publication date if available
- Authors
-
Ayako Ura, Takuo Hayashi, Kazumasa Komura, Masaki Hosoya, Kazuya Takamochi, Eiichi Sato, Satomi Saito, Susumu Wakai, Takafumi Handa, Tsuyoshi Saito, Shunsuke Kato, Kenji Suzuki, Takashi YaoList of authors in order
- Landing page
-
https://doi.org/10.1002/cjp2.350Publisher landing page
- PDF URL
-
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cjp2.350Direct link to full text PDF
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cjp2.350Direct OA link when available
- Concepts
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Copy-number variation, Cancer research, Biomarker, Gene dosage, Immunohistochemistry, Pathology, Biology, Fluorescence in situ hybridization, Medicine, Gene expression, Gene, Chromosome, Genome, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
1Total citation count in OpenAlex
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2024: 1Per-year citation counts (last 5 years)
- References (count)
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43Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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