TY - JOUR
T1 - Identification of novel prognostic and predictive biomarkers in salivary duct carcinoma via comprehensive molecular profiling
AU - Kohsaka, Shinji
AU - Tada, Yuichiro
AU - Ando, Mizuo
AU - Nakaguro, Masato
AU - Shirai, Yukina
AU - Ueno, Toshihide
AU - Kojima, Shinya
AU - Hirai, Hideaki
AU - Saigusa, Natsuki
AU - Kano, Satoshi
AU - Tsukahara, Kiyoaki
AU - Togashi, Takafumi
AU - Ozawa, Hiroyuki
AU - Kondo, Takahito
AU - Okami, Kenji
AU - Takahashi, Hideaki
AU - Kawakita, Daisuke
AU - Fushimi, Chihiro
AU - Suzuki, Takayoshi
AU - Shimizu, Akira
AU - Okamoto, Isaku
AU - Okada, Takuro
AU - Sato, Yuichiro
AU - Imanishi, Yorihisa
AU - Watanabe, Yoshihiro
AU - Sakai, Akihiro
AU - Ebisumoto, Koji
AU - Sato, Yukiko
AU - Urano, Makoto
AU - Honma, Yoshitaka
AU - Yamazaki, Keisuke
AU - Ueki, Yushi
AU - Hanazawa, Toyoyuki
AU - Saito, Yuki
AU - Shimura, Tomotaka
AU - Nagao, Toshitaka
AU - Mano, Hiroyuki
N1 - Funding Information:
The authors would like to thank Y. Yamamoto and A. Maruyama-Shiino for technical assistance. This study was supported by the grants from the Project for Cancer Research And Therapeutic Evolution (P-CREATE) under grant number JP20cm0106502, and the Practical Research for Innovative Cancer Control under grant number JP20ck0106536 from the Japan Agency for Medical Research and Development, AMED. This work was also supported by the JSPS Grants-in-Aid for Scientific Research (C) under grant number 18K09386 and 20K07417.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41698-022-00324-1
DO - 10.1038/s41698-022-00324-1
M3 - Article
AN - SCOPUS:85141159396
SN - 2397-768X
VL - 6
JO - npj Precision Oncology
JF - npj Precision Oncology
IS - 1
M1 - 82
ER -
