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 ShimizuIsaku 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number82
Journalnpj Precision Oncology
Volume6
Issue number1
DOIs
Publication statusPublished - 2022 Dec

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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