npj Precision Oncology (Nov 2022)
Identification of novel prognostic and predictive biomarkers in salivary duct carcinoma via comprehensive molecular profiling
- Shinji Kohsaka,
- Yuichiro Tada,
- Mizuo Ando,
- Masato Nakaguro,
- Yukina Shirai,
- Toshihide Ueno,
- Shinya Kojima,
- Hideaki Hirai,
- Natsuki Saigusa,
- Satoshi Kano,
- Kiyoaki Tsukahara,
- Takafumi Togashi,
- Hiroyuki Ozawa,
- Takahito Kondo,
- Kenji Okami,
- Hideaki Takahashi,
- Daisuke Kawakita,
- Chihiro Fushimi,
- Takayoshi Suzuki,
- Akira Shimizu,
- Isaku Okamoto,
- Takuro Okada,
- Yuichiro Sato,
- Yorihisa Imanishi,
- Yoshihiro Watanabe,
- Akihiro Sakai,
- Koji Ebisumoto,
- Yukiko Sato,
- Makoto Urano,
- Yoshitaka Honma,
- Keisuke Yamazaki,
- Yushi Ueki,
- Toyoyuki Hanazawa,
- Yuki Saito,
- Tomotaka Shimura,
- Toshitaka Nagao,
- Hiroyuki Mano
Affiliations
- Shinji Kohsaka
- Division of Cellular Signaling, National Cancer Center Research Institute
- Yuichiro Tada
- Department of Head and Neck Oncology and Surgery, International University of Health and Welfare, Mita Hospital
- Mizuo Ando
- Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
- Masato Nakaguro
- Department of Pathology and Laboratory Medicine, Nagoya University Hospital
- Yukina Shirai
- Division of Cellular Signaling, National Cancer Center Research Institute
- Toshihide Ueno
- Division of Cellular Signaling, National Cancer Center Research Institute
- Shinya Kojima
- Division of Cellular Signaling, National Cancer Center Research Institute
- Hideaki Hirai
- Department of Anatomic Pathology, Tokyo Medical University
- Natsuki Saigusa
- Department of Anatomic Pathology, Tokyo Medical University
- Satoshi Kano
- Department of Otolaryngology Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University
- Kiyoaki Tsukahara
- Department of Otolaryngology Head and Neck Surgery, Tokyo Medical University
- Takafumi Togashi
- Department of Head and Neck Surgery, Niigata Cancer Center Hospital
- Hiroyuki Ozawa
- Department of Otolaryngology Head and Neck Surgery, Keio University School of Medicine
- Takahito Kondo
- Department of Otolaryngology Head and Neck Surgery, Tokyo Medical University Hachioji Medical Center
- Kenji Okami
- Department of Otolaryngology Head and Neck Surgery, Tokai University School of Medicine
- Hideaki Takahashi
- Department of Otolaryngology, Head and Neck Surgery, Yokohama City University School of Medicine
- Daisuke Kawakita
- Department of Otolaryngology Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences
- Chihiro Fushimi
- Department of Head and Neck Oncology and Surgery, International University of Health and Welfare, Mita Hospital
- Takayoshi Suzuki
- Department of Otolaryngology Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University
- Akira Shimizu
- Department of Otolaryngology Head and Neck Surgery, Tokyo Medical University
- Isaku Okamoto
- Department of Otolaryngology Head and Neck Surgery, Tokyo Medical University
- Takuro Okada
- Department of Otolaryngology Head and Neck Surgery, Tokyo Medical University
- Yuichiro Sato
- Department of Otolaryngology and Head and Neck Surgery, School of Life Dentistry at Niigata, The Nippon Dental University
- Yorihisa Imanishi
- Department of Otolaryngology Head and Neck Surgery, Keio University School of Medicine
- Yoshihiro Watanabe
- Department of Otolaryngology Head and Neck Surgery, Keio University School of Medicine
- Akihiro Sakai
- Department of Otolaryngology Head and Neck Surgery, Tokai University School of Medicine
- Koji Ebisumoto
- Department of Otolaryngology Head and Neck Surgery, Tokai University School of Medicine
- Yukiko Sato
- Division of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research
- Makoto Urano
- Department of Diagnostic Pathology Bantane Hospital Fujita Health University, School of Medicine
- Yoshitaka Honma
- Department of Head & Neck, Esophageal Medical Oncology, National Cancer Center Hospital
- Keisuke Yamazaki
- Department of Otolaryngology Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences
- Yushi Ueki
- Department of Otolaryngology Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences
- Toyoyuki Hanazawa
- Department of Otorhinolaryngology/Head & Neck Surgery, Chiba University Graduate School of Medicine
- Yuki Saito
- Department of Otolaryngology - Head and Neck Surgery, Faculty of Medicine, The University of Tokyo
- Tomotaka Shimura
- Department of Otorhinolaryngology, Showa University Fujigaoka Hospital
- Toshitaka Nagao
- Department of Anatomic Pathology, Tokyo Medical University
- Hiroyuki Mano
- Division of Cellular Signaling, National Cancer Center Research Institute
- DOI
- https://doi.org/10.1038/s41698-022-00324-1
- Journal volume & issue
-
Vol. 6,
no. 1
pp. 1 – 12
Abstract
Abstract Molecular targets and predictive biomarkers for prognosis in salivary duct carcinoma (SDC) have not been fully identified. We conducted comprehensive molecular profiling to discover novel biomarkers for SDC. A total of 67 SDC samples were examined with DNA sequencing of 464 genes and transcriptome analysis in combination with the clinicopathological characteristics of the individuals. Prognostic biomarkers associated with response to combined androgen blockade (CAB) treatment were explored using mRNA expression data from 27 cases. Oncogenic mutations in receptor tyrosine kinase (RTK) genes or genes in the MAPK pathway were identified in 55 cases (82.1%). Alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway were identified in 38 cases (56.7%). Interestingly, patient prognosis could be predicted using mRNA expression profiles, but not genetic mutation profiles. The risk score generated from the expression data of a four-gene set that includes the ADAMTS1, DSC1, RNF39, and IGLL5 genes was a significant prognostic marker for overall survival in the cohort (HR = 5.99, 95% confidence interval (CI) = 2.73–13.1, p = 7.8 × 10−6). Another risk score constructed from the expression of CD3E and LDB3 was a strong prognostic marker for progression-free survival for CAB treatment (p = 0.03). Mutations in RTK genes, MAPK pathway genes, and PI3K/AKT pathway genes likely represent key mutations in SDC tumorigenesis. The gene expression profiles identified in this study may be useful for stratifying patients who are good candidates for CAB treatment and may benefit from additional systemic therapies.
