{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:54:39Z","timestamp":1788256479420,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61911530695"],"award-info":[{"award-number":["61911530695"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Breast cancer is one of the major cancers of women in the world. Despite significant progress in its treatment, an early diagnosis can effectively reduce its incidence rate and mortality. To improve the reliability of Raman-based tumor detection and analysis methods, we conducted an ex vivo study to unveil the compositional features of healthy control (HC), solid papillary carcinoma (SPC), mucinous carcinoma (MC), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissue samples. Following the identification of biological variations occurring as a result of cancer invasion, principal component analysis followed by linear discriminate analysis (PCA-LDA) algorithm were adopted to distinguish spectral variations among different breast tissue groups. The achieved results confirmed that after training, the constructed classification model combined with the leave-one-out cross-validation (LOOCV) method was able to distinguish the different breast tissue types with 100% overall accuracy. The present study demonstrates that Raman spectroscopy combined with multivariate analysis technology has considerable potential for improving the efficiency and performance of breast cancer diagnosis.<\/jats:p>","DOI":"10.3390\/molecules26040921","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T02:08:12Z","timestamp":1613268492000},"page":"921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Raman Microspectroscopic Investigation and Classification of Breast Cancer Pathological Characteristics"],"prefix":"10.3390","volume":"26","author":[{"given":"Heping","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon-Technology, Northwest University, Xi\u2019an 710127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Ning","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon-Technology, Northwest University, Xi\u2019an 710127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon-Technology, Northwest University, Xi\u2019an 710127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishen","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon-Technology, Northwest University, Xi\u2019an 710127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoping","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon-Technology, Northwest University, Xi\u2019an 710127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5558-4029","authenticated-orcid":false,"given":"Shuang","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon-Technology, Northwest University, Xi\u2019an 710127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3322\/caac.21349","article-title":"Cancer treatment and survivorship statistics, 2016","volume":"66","author":"Miller","year":"2016","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3322\/caac.20138","article-title":"Cancer statistics, 2012","volume":"62","author":"Siegel","year":"2012","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"106475","DOI":"10.1016\/j.prostaglandins.2020.106475","article-title":"Accurate identification of breast cancer margins in microenvironments of ex-vivo basal and luminal breast cancer tissues using Raman spectroscopy","volume":"151","author":"Koya","year":"2020","journal-title":"Prostag. Other Lipid Mediat."},{"key":"ref_4","first-page":"1","article-title":"A review of the applications of Raman spectroscopy for breast cancer tissue diagnostic and their histopathological classification of epithelial to mesenchymal transition","volume":"51","author":"Sabtu","year":"2019","journal-title":"J. Raman Spectrosc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1039\/C5AN02073E","article-title":"Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity","volume":"141","author":"Zhao","year":"2016","journal-title":"Analyst"},{"key":"ref_6","first-page":"2353","article-title":"Breast-Cancer Screening\u2014Viewpoint of the IARC Working Group","volume":"373","author":"Scoccianti","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1002\/cncr.11222","article-title":"Positive surgical margins and ipsilateral breast tumor recurrence predict disease-specific survival after breast-conserving therapy","volume":"97","author":"Evans","year":"2003","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e4505","DOI":"10.1136\/bmj.e4505","article-title":"Reoperation rates after breast conserving surgery for breast cancer among women in England: Retrospective study of hospital episode statistics","volume":"345","author":"Jeevan","year":"2012","journal-title":"BMJ"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1001\/jama.2012.43","article-title":"Variability in Reexcision Following Breast Conservation Surgery","volume":"307","author":"Mccahill","year":"2012","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s40137-016-0136-3","article-title":"Advances in Intraoperative Margin Assessment for Breast Cancer","volume":"4","author":"Keating","year":"2016","journal-title":"Curr. Surg. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1309\/AJCPRSOA2G8RLEXY","article-title":"Is Intraoperative Frozen Section Analysis of Reexcision Specimens of Value in Preventing Reoperation in Breast-Conserving Therapy?","volume":"142","author":"Jorns","year":"2014","journal-title":"Am.J. Clin. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1097\/SLA.0000000000000622","article-title":"The status of contemporary image-guided modalities in oncologic surgery","volume":"261","author":"Rosenthal","year":"2015","journal-title":"Ann. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1245\/s10434-007-9364-1","article-title":"Intraoperative Touch Preparation Cytology for Margin Assessment in Breast-Conservation Surgery: Does It Work for Lobular Carcinoma?","volume":"14","author":"Valdes","year":"2007","journal-title":"Ann. Surg. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.1039\/c3an00698k","article-title":"Illuminating disease and enlightening biomedicine: Raman spectroscopy as a diagnostic tool","volume":"138","author":"David","year":"2013","journal-title":"Analyst"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1080\/05704920701551530","article-title":"Raman Spectroscopy of Biological Tissues","volume":"42","author":"Movasaghi","year":"2007","journal-title":"Appl. Spectrosc. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/s10555-018-9770-9","article-title":"Applications of Raman spectroscopy in cancer diagnosis","volume":"37","author":"Auner","year":"2018","journal-title":"Cancer Metast. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1364\/BOE.383869","article-title":"Raman spectroscopy combined with multivariate analysis to study the biochemical mechanism of lung cancer microwave ablation","volume":"11","author":"Song","year":"2020","journal-title":"Biomed. Opt. Express"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1039\/C9AN01524H","article-title":"Study on the biochemical mechanisms of the micro-wave ablation treatment of lung cancer by ex vivo confocal Raman microspectral imaging","volume":"145","author":"Song","year":"2020","journal-title":"Analyst"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1039\/C7AN00957G","article-title":"Raman spectroscopy for cancer detection and cancer surgery guidance: Translation to the clinics","volume":"142","author":"Santos","year":"2017","journal-title":"Analyst"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"024013","DOI":"10.1117\/1.2899155","article-title":"Raman microspectroscopy for skin cancer detection in vitro","volume":"13","author":"Lieber","year":"2008","journal-title":"J. Biomed. Opt."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1158\/0008-5472.CAN-19-3204","article-title":"Raman Spectroscopy Reveals That Biochemical Composition of Breast Microcalcifications Correlates with Histopathologic Features","volume":"80","author":"Vanna","year":"2020","journal-title":"Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s13058-018-1002-2","article-title":"Intra-operative spectroscopic assessment of surgical margins during breast conserving surgery","volume":"20","author":"Shipp","year":"2018","journal-title":"Breast Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.jbi.2013.06.014","article-title":"Semi-supervised clinical text classification with Laplacian SVMs: An application to cancer case management","volume":"46","author":"Garla","year":"2013","journal-title":"J. Biomed. Inform."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1038\/sj.bjc.6603102","article-title":"Raman spectroscopy: Elucidation of biochemical changes in carcinogenesis of oesophagus","volume":"94","author":"Shetty","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"22892","DOI":"10.1364\/OE.19.022892","article-title":"Full range characterization of the Raman spectra of organs in a murine model","volume":"19","author":"Huang","year":"2011","journal-title":"Opt. Express"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1002\/bip.20398","article-title":"Discrimination of normal, inflammatory, premalignant, and malignant oral tissue: A Raman spectroscopy study","volume":"81","author":"Malini","year":"2010","journal-title":"Biopolymers"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1177\/0003702816681009","article-title":"Differences and Relationships Between Normal and Atypical Ductal Hyperplasia, Ductal Carcinoma In Situ, and Invasive Ductal Carcinoma Tissues in the Breast Based on Raman Spectroscopy","volume":"71","author":"Han","year":"2017","journal-title":"Appl. Spectrosc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1667\/0033-7587(2002)157[0175:TRSFTS]2.0.CO;2","article-title":"Tissue Raman spectroscopy for the study of radiation damage: Brain irradiation of mice","volume":"157","author":"Lakshmi","year":"2002","journal-title":"Radiat. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1039\/b304992b","article-title":"Raman spectroscopy for identification of epithelial cancers","volume":"126","author":"Stone","year":"2004","journal-title":"Faraday Discuss."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7958","DOI":"10.1021\/ac0512599","article-title":"Detection of Meningioma in Dura Mater by Raman Spectroscopy","volume":"77","author":"Koljenovic","year":"2005","journal-title":"Anal. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1002\/ijc.11500","article-title":"Near-infrared Raman spectroscopy for optical diagnosis of lung cancer","volume":"107","author":"Huang","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1073\/pnas.0707654105","article-title":"Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy","volume":"105","author":"Liu","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1366\/000370210790918364","article-title":"Near-Infrared Micro-Raman Spectroscopy for in Vitro Detection of Cervical Cancer","volume":"64","author":"Kamemoto","year":"2010","journal-title":"Appl. Spectrosc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1002\/jrs.5360","article-title":"In vivo Raman spectroscopy of breast tumors prephotodynamic and postphotodynamic therapy","volume":"49","author":"Bhattacharjee","year":"2018","journal-title":"J. Raman Spectrosc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.molliq.2008.02.015","article-title":"Breast cancer diagnostics by Raman spectroscopy","volume":"141","author":"Brozekpluska","year":"2008","journal-title":"J. Mol. Liq."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1039\/C1AN15821J","article-title":"Understanding the molecular information contained in principal component analysis of vibrational spectra of biological systems","volume":"137","author":"Bonnier","year":"2012","journal-title":"Analyst"},{"key":"ref_37","first-page":"93","article-title":"Characterization by Raman spectroscopy of conformational changes on guanine\u2013cytosine and adenine\u2013thymine oligonucleotides induced by aminooxy analogues of spermidine","volume":"35","author":"Medina","year":"2010","journal-title":"J. Raman Spectrosc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jphotobiol.2016.08.032","article-title":"Confocal raman microspectral imaging of ex vivo human spinal cord tissue","volume":"163","author":"Wang","year":"2016","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1155\/2010\/592315","article-title":"A modular Raman microspectroscopy system for biological tissue analysis","volume":"24","author":"Wang","year":"2010","journal-title":"Spectroscopy"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1111\/j.1751-1097.1996.tb05671.x","article-title":"The effects of ex vivo handling procedures on the near-infrared Raman spectra of normal mammalian tissues","volume":"63","author":"Shim","year":"1996","journal-title":"Photochem. Photobiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Li, J., Qin, J., Zeng, H., Li, J., and Wang, S. (2020). Unveiling doseand time \u03b3: Ependent osteosarcoma cell responses to the \u03b3: Ecretase inhibitor, DAPT, by confocal Raman microscopy. J. Biophoton.","DOI":"10.1002\/jbio.202000238"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"118372","DOI":"10.1016\/j.saa.2020.118372","article-title":"Confocal Raman microspectroscopic analysis on the time-dependent impact of DAPT, a \u03b3-secretase inhibitor, to osteosarcoma cells","volume":"239","author":"Li","year":"2020","journal-title":"Spectrochim. Acta A"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1016\/j.bios.2010.03.033","article-title":"Nasopharyngeal cancer detection based on blood plasma surface-enhanced Raman spectroscopy and multivariate analysis","volume":"25","author":"Feng","year":"2010","journal-title":"Biosens. Bioelectron."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/4\/921\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:22:09Z","timestamp":1760160129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/4\/921"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,9]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["molecules26040921"],"URL":"https:\/\/doi.org\/10.3390\/molecules26040921","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,9]]}}}