Spatial Transcriptomics Reveals HER2/AR-Associated Heterogeneity and Alternative Surface Targets in Salivary Duct Carcinoma
- 1Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Shinshu University, 3-1-1, Asahi, Matsumoto City 390-8621, Japan
- 2Department of Laboratory Medicine, School of Medicine, Shinshu University, 3-1-1, Asahi, Matsumoto City 390-8621, Japan
Abstract
Salivary duct carcinoma (SDC) is an aggressive malignancy primarily treated with human epidermal growth factor receptor 2 (HER2)- and androgen receptor (AR)-directed therapies in the recurrent or metastatic setting, although therapeutic responses remain heterogeneous. We used spatial transcriptomics to characterize intratumoral heterogeneity and to identify alternative therapeutic targets. Spatial transcriptomic profiling was performed on four formalin-fixed, paraffin-embedded SDC specimens using the 10× Genomics Visium platform. Tumor regions were characterized according to spatial HER2 and AR expression and their corresponding transcriptional signatures. Candidate cell-surface targets in HER2/AR-non-associated regions were identified using the SURFY human surfaceome and prioritized based on low expression in matched normal salivary gland tissue and therapeutic relevance. Spatial mapping revealed heterogeneous distributions of HER2- and AR-associated transcriptional states within individual tumors, including HER2/AR-non-associated regions in all four specimens. Surfaceome screening identified several candidate targets with low expression in matched normal salivary gland tissue, among which ALCAM showed consistently broad whole-tumor coverage across all four specimens. These findings highlight substantial intratumoral heterogeneity in SDC and identify alternative cell-surface targets that may complement HER2- and AR-directed therapies.
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BibTeX
@article{iwasa2026spatial,
title = {{Spatial Transcriptomics Reveals HER2/AR-Associated Heterogeneity and Alternative Surface Targets in Salivary Duct Carcinoma}},
author = {Yoh-ichiro Iwasa and Kentaro Hori and Tomoyuki Nakajima and Yoh Yokota and Shintaro Yamazaki and Yukiko Hori and Takeshi Uehara and Yutaka Takumi},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209018},
url = {https://www.mdpi.com/1422-0067/27/20/9018},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Spatial Transcriptomics Reveals HER2/AR-Associated Heterogeneity and Alternative Surface Targets in Salivary Duct Carcinoma
AU - Yoh-ichiro Iwasa
AU - Kentaro Hori
AU - Tomoyuki Nakajima
AU - Yoh Yokota
AU - Shintaro Yamazaki
AU - Yukiko Hori
AU - Takeshi Uehara
AU - Yutaka Takumi
PY - 2026
DA - 2026/10/12
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209018
UR - https://www.mdpi.com/1422-0067/27/20/9018
AB - Salivary duct carcinoma (SDC) is an aggressive malignancy primarily treated with human epidermal growth factor receptor 2 (HER2)- and androgen receptor (AR)-directed therapies in the recurrent or metastatic setting, although therapeutic responses remain heterogeneous. We used spatial transcriptomics to characterize intratumoral heterogeneity and to identify alternative therapeutic targets. Spatial transcriptomic profiling was performed on four formalin-fixed, paraffin-embedded SDC specimens using the 10× Genomics Visium platform. Tumor regions were characterized according to spatial HER2 and AR expression and their corresponding transcriptional signatures. Candidate cell-surface targets in HER2/AR-non-associated regions were identified using the SURFY human surfaceome and prioritized based on low expression in matched normal salivary gland tissue and therapeutic relevance. Spatial mapping revealed heterogeneous distributions of HER2- and AR-associated transcriptional states within individual tumors, including HER2/AR-non-associated regions in all four specimens. Surfaceome screening identified several candidate targets with low expression in matched normal salivary gland tissue, among which ALCAM showed consistently broad whole-tumor coverage across all four specimens. These findings highlight substantial intratumoral heterogeneity in SDC and identify alternative cell-surface targets that may complement HER2- and AR-directed therapies.
SN - 1422-0067
ER -