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

doi:10.1038/s41698-022-00324-1

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

Diagnostic pathology

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

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 language	English
Article number	82
Journal	npj Precision Oncology
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s41698-022-00324-1
Publication status	Published - 12-2022

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41698-022-00324-1

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Kohsaka, S., Tada, Y., Ando, M., Nakaguro, M., Shirai, Y., Ueno, T., Kojima, S., Hirai, H., Saigusa, N., Kano, S., Tsukahara, K., Togashi, T., Ozawa, H., Kondo, T., Okami, K., Takahashi, H., Kawakita, D., Fushimi, C., Suzuki, T., ... Mano, H. (2022). Identification of novel prognostic and predictive biomarkers in salivary duct carcinoma via comprehensive molecular profiling. npj Precision Oncology, 6(1), Article 82. https://doi.org/10.1038/s41698-022-00324-1

@article{3823ebb2321a4b56b0ad44780cb8bc85,

title = "Identification of novel prognostic and predictive biomarkers in salivary duct carcinoma via comprehensive molecular profiling",

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.",

author = "Shinji Kohsaka and Yuichiro Tada and Mizuo Ando and Masato Nakaguro and Yukina Shirai and Toshihide Ueno and Shinya Kojima and Hideaki Hirai and Natsuki Saigusa and Satoshi Kano and Kiyoaki Tsukahara and Takafumi Togashi and Hiroyuki Ozawa and Takahito Kondo and Kenji Okami and Hideaki Takahashi and Daisuke Kawakita and Chihiro Fushimi and Takayoshi Suzuki and Akira Shimizu and Isaku Okamoto and Takuro Okada and Yuichiro Sato and Yorihisa Imanishi and Yoshihiro Watanabe and Akihiro Sakai and Koji Ebisumoto and Yukiko Sato and Makoto Urano and Yoshitaka Honma and Keisuke Yamazaki and Yushi Ueki and Toyoyuki Hanazawa and Yuki Saito and Tomotaka Shimura and Toshitaka Nagao and Hiroyuki Mano",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41698-022-00324-1",

language = "English",

volume = "6",

journal = "npj Precision Oncology",

issn = "2397-768X",

publisher = "Springer Nature",

number = "1",

}

Kohsaka, S, Tada, Y, Ando, M, Nakaguro, M, Shirai, Y, Ueno, T, Kojima, S, Hirai, H, Saigusa, N, Kano, S, Tsukahara, K, Togashi, T, Ozawa, H, Kondo, T, Okami, K, Takahashi, H, Kawakita, D, Fushimi, C, Suzuki, T, Shimizu, A, Okamoto, I, Okada, T, Sato, Y, Imanishi, Y, Watanabe, Y, Sakai, A, Ebisumoto, K, Sato, Y, Urano, M, Honma, Y, Yamazaki, K, Ueki, Y, Hanazawa, T, Saito, Y, Shimura, T, Nagao, T & Mano, H 2022, 'Identification of novel prognostic and predictive biomarkers in salivary duct carcinoma via comprehensive molecular profiling', npj Precision Oncology, vol. 6, no. 1, 82. https://doi.org/10.1038/s41698-022-00324-1

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

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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UR - http://www.scopus.com/inward/citedby.url?scp=85141159396&partnerID=8YFLogxK

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 -

Identification of novel prognostic and predictive biomarkers in salivary duct carcinoma via comprehensive molecular profiling

Abstract

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