{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:28:58Z","timestamp":1791606538254,"version":"4.3.4"},"reference-count":29,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JST ERATO Suematsu Gas Biology Project","award":["JP22zf0127007"],"award-info":[{"award-number":["JP22zf0127007"]}]},{"name":"JST ERATO Suematsu Gas Biology Project","award":["WPI-Bio2Q"],"award-info":[{"award-number":["WPI-Bio2Q"]}]},{"name":"JST Moonshot Project for Cancer Research","award":["JP22zf0127007"],"award-info":[{"award-number":["JP22zf0127007"]}]},{"name":"JST Moonshot Project for Cancer Research","award":["WPI-Bio2Q"],"award-info":[{"award-number":["WPI-Bio2Q"]}]},{"name":"AMED-Moonshot","award":["JP22zf0127007"],"award-info":[{"award-number":["JP22zf0127007"]}]},{"name":"AMED-Moonshot","award":["WPI-Bio2Q"],"award-info":[{"award-number":["WPI-Bio2Q"]}]},{"name":"Human Biology Microbiome Quantum Research Center","award":["JP22zf0127007"],"award-info":[{"award-number":["JP22zf0127007"]}]},{"name":"Human Biology Microbiome Quantum Research Center","award":["WPI-Bio2Q"],"award-info":[{"award-number":["WPI-Bio2Q"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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 (n = 14) and IBC (n = 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.<\/jats:p>","DOI":"10.3390\/antiox12020240","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T03:21:54Z","timestamp":1674616914000},"page":"240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Polysulfide Serves as a Hallmark of Desmoplastic Reaction to Differentially Diagnose Ductal Carcinoma In Situ and Invasive Breast Cancer by SERS Imaging"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6003-227X","authenticated-orcid":false,"given":"Akiko","family":"Kubo","sequence":"first","affiliation":[{"name":"Departments of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6952-4043","authenticated-orcid":false,"given":"Yohei","family":"Masugi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Hase","sequence":"additional","affiliation":[{"name":"The Systems Biology Institute, Tokyo 141-0022, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4529-9045","authenticated-orcid":false,"given":"Kengo","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Kawai","sequence":"additional","affiliation":[{"name":"Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minako","family":"Takizawa","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Hishiki","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8875-8865","authenticated-orcid":false,"given":"Megumi","family":"Shiota","sequence":"additional","affiliation":[{"name":"Analysis Technology Center, CTO Office, FUJIFILM Corporation, Minamiashigara-shi 250-0193, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Wakui","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuaki","family":"Kabe","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiie","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Yachie","sequence":"additional","affiliation":[{"name":"The Systems Biology Institute, Tokyo 141-0022, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsu","family":"Hayashida","sequence":"additional","affiliation":[{"name":"Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Suematsu","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, Japan"},{"name":"Live Imaging Center, Central Institute for Experimental Animals, Kawasaki-shi 210-0821, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2027738","DOI":"10.1001\/jamanetworkopen.2020.27738","article-title":"Trends in Cancer Incidence in US Adolescents and Young Adults, 1973\u20132015","volume":"3","author":"Scott","year":"2020","journal-title":"JAMA Netw. 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