The Influence of the Germline HSD3B1 Adrenal-Permissive Allele (c.1100 C) on the Somatic Alteration Landscape, the Transcriptome, and Immune Cell Infiltration in Prostate Cancer Article Swipe
Samuel Kellen
,
Allison Makovec
,
Carly D. Miller
,
Shayan Nazari
,
Andrew Elliott
,
Aiden Deacon
,
Emily John
,
Nikitha Vobugari
,
Neeraj Agarwal
,
Rana R. McKay
,
Pedro C. Barata
,
Charles J. Ryan
,
Nima Sharifi
,
Justin H. Hwang
,
Emmanuel S. Antonarakis
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/cancers17081270
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/cancers17081270
Background/Objectives: The germline polymorphism in the HSD3B1 gene (c.1100 C) results in adrenal-permissive (CC) or adrenal-restrictive (AA) functions of the protein product by regulating the production of high-affinity ligands that activate androgen signaling. Prior studies have indicated that the CC genotype is associated with worse response to hormonal therapies in prostate cancer (PC) patients. Methods: To characterize the impact of germline HSD3B1 variants on somatic tumor features, we examined 6550 primary and metastatic PCs from the Caris Life Sciences database, in which the genomic and transcriptomic landscapes were acquired via paired whole-exome/whole-transcriptome sequencing. Results: The overall prevalence of the HSD3B1 AA genotype (restrictive–homozygous) was 48.8%, AC (permissive–heterozygous) was 32.8%, and CC (permissive–homozygous) was 14.9%. There was enrichment of the CC genotype in these PC patients as compared to prior reports that examined non-cancerous populations. However, the rates of the CC genotype varied between metastatic site and by race. Compared to the AA genotype, tumors harboring the CC genotype did not demonstrate increased AR alterations, nor higher expression of AR, FOXA1, HOXB13, or AR signaling signatures. We instead found significant changes in immune-associated hallmark pathways, immune cell fractions, and biomarkers that inform the use of immune therapies (TMB-high, MSI-high). Further, the CC and AA genotypes exhibited notable differences in the expression of immunoglobulins, MHC class I/II molecules, and cell surface targets. The differences in expression by HSD3B1 genotype were especially notable in lung and liver metastases. Conclusions: Our study indicates that in prostate cancers, HSD3B1 germline c.1100 allele status may not directly influence tumor-intrinsic genomics but is associated with novel functions beyond androgen signaling.
Related Topics
Concepts
Genotype
Transcriptome
Biology
Immune system
Germline
Permissive
Cancer research
Allele
Prostate cancer
MHC class I
Genetics
Gene
Cancer
Gene expression
Major histocompatibility complex
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/cancers17081270
- https://www.mdpi.com/2072-6694/17/8/1270/pdf?version=1744190872
- OA Status
- gold
- Cited By
- 1
- References
- 30
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4409282329
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4409282329Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3390/cancers17081270Digital Object Identifier
- Title
-
The Influence of the Germline HSD3B1 Adrenal-Permissive Allele (c.1100 C) on the Somatic Alteration Landscape, the Transcriptome, and Immune Cell Infiltration in Prostate CancerWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-04-09Full publication date if available
- Authors
-
Samuel Kellen, Allison Makovec, Carly D. Miller, Shayan Nazari, Andrew Elliott, Aiden Deacon, Emily John, Nikitha Vobugari, Neeraj Agarwal, Rana R. McKay, Pedro C. Barata, Charles J. Ryan, Nima Sharifi, Justin H. Hwang, Emmanuel S. AntonarakisList of authors in order
- Landing page
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https://doi.org/10.3390/cancers17081270Publisher landing page
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https://www.mdpi.com/2072-6694/17/8/1270/pdf?version=1744190872Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.mdpi.com/2072-6694/17/8/1270/pdf?version=1744190872Direct OA link when available
- Concepts
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Genotype, Transcriptome, Biology, Immune system, Germline, Permissive, Cancer research, Allele, Prostate cancer, MHC class I, Genetics, Gene, Cancer, Gene expression, Major histocompatibility complexTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
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2025: 1Per-year citation counts (last 5 years)
- References (count)
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30Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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