Polysulfide Serves as a Hallmark of Desmoplastic Reaction to Differentially Diagnose Ductal Carcinoma In Situ and Invasive Breast Cancer by SERS Imaging
Pathological examination of formalin-fixed paraffin-embedded (FFPE) needle-biopsied samples by certified pathologists represents the gold standard for differential diagnosis between ductal carcinoma in situ (DCIS) and invasive breast cancers (IBC), while information of marker metabolites in the samp...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/2/240 |
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| author | Akiko Kubo Yohei Masugi Takeshi Hase Kengo Nagashima Yuko Kawai Minako Takizawa Takako Hishiki Megumi Shiota Masatoshi Wakui Yuko Kitagawa Yasuaki Kabe Michiie Sakamoto Ayako Yachie Tetsu Hayashida Makoto Suematsu |
| author_facet | Akiko Kubo Yohei Masugi Takeshi Hase Kengo Nagashima Yuko Kawai Minako Takizawa Takako Hishiki Megumi Shiota Masatoshi Wakui Yuko Kitagawa Yasuaki Kabe Michiie Sakamoto Ayako Yachie Tetsu Hayashida Makoto Suematsu |
| author_sort | Akiko Kubo |
| collection | DOAJ |
| description | Pathological examination of formalin-fixed paraffin-embedded (FFPE) needle-biopsied samples by certified pathologists represents the gold standard for differential diagnosis between ductal carcinoma in situ (DCIS) and invasive breast cancers (IBC), while information of marker metabolites in the samples is lost in the samples. Infrared laser-scanning large-area surface-enhanced Raman spectroscopy (SERS) equipped with gold-nanoparticle-based SERS substrate enables us to visualize metabolites in fresh-frozen needle-biopsied samples with spatial matching between SERS and HE staining images with pathological annotations. DCIS (<i>n</i> = 14) and IBC (<i>n</i> = 32) samples generated many different SERS peaks in finger-print regions of SERS spectra among pathologically annotated lesions including cancer cell nests and the surrounding stroma. The results showed that SERS peaks in IBC stroma exhibit significantly increased polysulfide that coincides with decreased hypotaurine as compared with DCIS, suggesting that alterations of these redox metabolites account for fingerprints of desmoplastic reactions to distinguish IBC from DCIS. Furthermore, the application of supervised machine learning to the stroma-specific multiple SERS signals enables us to support automated differential diagnosis with high accuracy. The results suggest that SERS-derived biochemical fingerprints derived from redox metabolites account for a hallmark of desmoplastic reaction of IBC that is absent in DCIS, and thus, they serve as a useful method for precision diagnosis in breast cancer. |
| first_indexed | 2024-03-11T09:15:31Z |
| format | Article |
| id | doaj.art-ee9659f747144fcdaba90880cf161498 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T09:15:31Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-ee9659f747144fcdaba90880cf1614982023-11-16T18:45:20ZengMDPI AGAntioxidants2076-39212023-01-0112224010.3390/antiox12020240Polysulfide Serves as a Hallmark of Desmoplastic Reaction to Differentially Diagnose Ductal Carcinoma In Situ and Invasive Breast Cancer by SERS ImagingAkiko Kubo0Yohei Masugi1Takeshi Hase2Kengo Nagashima3Yuko Kawai4Minako Takizawa5Takako Hishiki6Megumi Shiota7Masatoshi Wakui8Yuko Kitagawa9Yasuaki Kabe10Michiie Sakamoto11Ayako Yachie12Tetsu Hayashida13Makoto Suematsu14Departments of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Pathology, Keio University School of Medicine, Tokyo 160-8582, JapanThe Systems Biology Institute, Tokyo 141-0022, JapanBiostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo 160-8582, JapanDepartment of Surgery, Keio University School of Medicine, Tokyo 160-8582, JapanDepartments of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, JapanDepartments of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, JapanAnalysis Technology Center, CTO Office, FUJIFILM Corporation, Minamiashigara-shi 250-0193, Kanagawa, JapanDepartment of Laboratory Medicine, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Surgery, Keio University School of Medicine, Tokyo 160-8582, JapanDepartments of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Pathology, Keio University School of Medicine, Tokyo 160-8582, JapanThe Systems Biology Institute, Tokyo 141-0022, JapanDepartment of Surgery, Keio University School of Medicine, Tokyo 160-8582, JapanDepartments of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, JapanPathological examination of formalin-fixed paraffin-embedded (FFPE) needle-biopsied samples by certified pathologists represents the gold standard for differential diagnosis between ductal carcinoma in situ (DCIS) and invasive breast cancers (IBC), while information of marker metabolites in the samples is lost in the samples. Infrared laser-scanning large-area surface-enhanced Raman spectroscopy (SERS) equipped with gold-nanoparticle-based SERS substrate enables us to visualize metabolites in fresh-frozen needle-biopsied samples with spatial matching between SERS and HE staining images with pathological annotations. DCIS (<i>n</i> = 14) and IBC (<i>n</i> = 32) samples generated many different SERS peaks in finger-print regions of SERS spectra among pathologically annotated lesions including cancer cell nests and the surrounding stroma. The results showed that SERS peaks in IBC stroma exhibit significantly increased polysulfide that coincides with decreased hypotaurine as compared with DCIS, suggesting that alterations of these redox metabolites account for fingerprints of desmoplastic reactions to distinguish IBC from DCIS. Furthermore, the application of supervised machine learning to the stroma-specific multiple SERS signals enables us to support automated differential diagnosis with high accuracy. The results suggest that SERS-derived biochemical fingerprints derived from redox metabolites account for a hallmark of desmoplastic reaction of IBC that is absent in DCIS, and thus, they serve as a useful method for precision diagnosis in breast cancer.https://www.mdpi.com/2076-3921/12/2/240breast cancerimaging metabolomicspolysulfidehypotaurineglutathione |
| spellingShingle | Akiko Kubo Yohei Masugi Takeshi Hase Kengo Nagashima Yuko Kawai Minako Takizawa Takako Hishiki Megumi Shiota Masatoshi Wakui Yuko Kitagawa Yasuaki Kabe Michiie Sakamoto Ayako Yachie Tetsu Hayashida Makoto Suematsu Polysulfide Serves as a Hallmark of Desmoplastic Reaction to Differentially Diagnose Ductal Carcinoma In Situ and Invasive Breast Cancer by SERS Imaging Antioxidants breast cancer imaging metabolomics polysulfide hypotaurine glutathione |
| title | Polysulfide Serves as a Hallmark of Desmoplastic Reaction to Differentially Diagnose Ductal Carcinoma In Situ and Invasive Breast Cancer by SERS Imaging |
| title_full | Polysulfide Serves as a Hallmark of Desmoplastic Reaction to Differentially Diagnose Ductal Carcinoma In Situ and Invasive Breast Cancer by SERS Imaging |
| title_fullStr | Polysulfide Serves as a Hallmark of Desmoplastic Reaction to Differentially Diagnose Ductal Carcinoma In Situ and Invasive Breast Cancer by SERS Imaging |
| title_full_unstemmed | Polysulfide Serves as a Hallmark of Desmoplastic Reaction to Differentially Diagnose Ductal Carcinoma In Situ and Invasive Breast Cancer by SERS Imaging |
| title_short | Polysulfide Serves as a Hallmark of Desmoplastic Reaction to Differentially Diagnose Ductal Carcinoma In Situ and Invasive Breast Cancer by SERS Imaging |
| title_sort | polysulfide serves as a hallmark of desmoplastic reaction to differentially diagnose ductal carcinoma in situ and invasive breast cancer by sers imaging |
| topic | breast cancer imaging metabolomics polysulfide hypotaurine glutathione |
| url | https://www.mdpi.com/2076-3921/12/2/240 |
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