Applying Proteogenomics to Characterize Molecular Features Associated With a High-Risk HOXB13 Gene Variant in Prostate Cancer Tumors.
4 affiliations
- 1Menzies Institute for Medical Research University of Tasmania Hobart Tasmania Australia.
- 2ProCan® Children's Medical Research Institute Faculty of Medicine and Health The University of Sydney Westmead New South Wales Australia.
- 3Melbourne Bioinformatics The University of Melbourne Parkville Victoria Australia.
- 4Sonic Healthcare Hobart Tasmania Australia.
Abstract
The rare HOXB13 G84E variant is one of few established high-risk prostate cancer (PrCa) variants, yet the underlying molecular mechanisms by which it drives tumor development remain unknown. Prostate tumors from six heterozygous G84E variant carriers and 18 non-carriers (wild-type) were examined using the Human AmpliSeq Transcriptome Gene Expression Panel, and proteomes were generated by mass spectrometry (SWATH). We identified a 799-gene expression profile and a 75-protein expression profile in G84E-positive tumors when compared with wild-type tumors. Cluster analysis revealed a top-ranked 23 protein profile, which mapped to lipogenesis pathways. Integration of transcriptome and proteome data revealed overlapping differential expression of three genes (NCLN, NFIB, and VASN), two of which have an established link to lipid metabolic pathways. Examination of publicly available transcriptome data from 493 primary PrCa tumors from the The Cancer Genome Atlas (TCGA) tumors revealed 52 tumors with a similar differential expression profile for these three genes. Herein, an innovative proteogenomic approach was used to map molecular changes unique to HOXB13 perturbation in prostate tumors, revealing upregulation of genes in the steroid metabolic, lipid biosynthesis, and fatty acid metabolic pathways.
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BibTeX
@article{raspin2026applying,
title = {{Applying Proteogenomics to Characterize Molecular Features Associated With a High-Risk HOXB13 Gene Variant in Prostate Cancer Tumors.}},
author = {Kelsie Raspin and Zainab Noor and Adel T Aref and James R Marthick and Chol-Hee Jung and Shaun Donovan and Steve Williams and Peter G Hains and Phillip J Robinson and Rosemary L Balleine and Qing Zhong and Roger R Reddel and Liesel M FitzGerald and Joanne L Dickinson},
journal = {MedComm},
year = {2026},
month = oct,
doi = {10.1002/mco2.71078},
url = {https://europepmc.org/article/MED/42922890},
note = {CC BY},
}
RIS
TY - JOUR
TI - Applying Proteogenomics to Characterize Molecular Features Associated With a High-Risk HOXB13 Gene Variant in Prostate Cancer Tumors.
AU - Kelsie Raspin
AU - Zainab Noor
AU - Adel T Aref
AU - James R Marthick
AU - Chol-Hee Jung
AU - Shaun Donovan
AU - Steve Williams
AU - Peter G Hains
AU - Phillip J Robinson
AU - Rosemary L Balleine
AU - Qing Zhong
AU - Roger R Reddel
AU - Liesel M FitzGerald
AU - Joanne L Dickinson
PY - 2026
DA - 2026/10/21
JO - MedComm
DO - 10.1002/mco2.71078
UR - https://europepmc.org/article/MED/42922890
AB - The rare HOXB13 G84E variant is one of few established high-risk prostate cancer (PrCa) variants, yet the underlying molecular mechanisms by which it drives tumor development remain unknown. Prostate tumors from six heterozygous G84E variant carriers and 18 non-carriers (wild-type) were examined using the Human AmpliSeq Transcriptome Gene Expression Panel, and proteomes were generated by mass spectrometry (SWATH). We identified a 799-gene expression profile and a 75-protein expression profile in G84E-positive tumors when compared with wild-type tumors. Cluster analysis revealed a top-ranked 23 protein profile, which mapped to lipogenesis pathways. Integration of transcriptome and proteome data revealed overlapping differential expression of three genes (NCLN, NFIB, and VASN), two of which have an established link to lipid metabolic pathways. Examination of publicly available transcriptome data from 493 primary PrCa tumors from the The Cancer Genome Atlas (TCGA) tumors revealed 52 tumors with a similar differential expression profile for these three genes. Herein, an innovative proteogenomic approach was used to map molecular changes unique to HOXB13 perturbation in prostate tumors, revealing upregulation of genes in the steroid metabolic, lipid biosynthesis, and fatty acid metabolic pathways.
SN - 2688-2663
ER -