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Herein, we report on three cases where Raman microspectroscopy was used to distinguish normal vs. oesophageal adenocarcinoma (OAC) (case 1) and Barrett\u2019s oesophagus vs. OAC (cases 2 and 3) in a non-destructive and highly accurate fashion. Normal and OAC tissues were discriminated using principal component analysis plus linear discriminant analysis (PCA-LDA) with 97% accuracy (94% sensitivity and 100% specificity) (case 1); Barrett\u2019s oesophagus vs. OAC tissues were discriminated with accuracies ranging from 98 to 100% (97\u2013100% sensitivity and 100% specificity). Spectral markers responsible for class differentiation were obtained through the difference-between-mean spectrum for each group and the PCA loadings, where C\u2013O\u2013C skeletal mode in \u03b2-glucose (900\u00a0cm<jats:sup>\u22121<\/jats:sup>), lipids (967\u00a0cm<jats:sup>\u22121<\/jats:sup>), phosphodioxy (1296\u00a0cm<jats:sup>\u22121<\/jats:sup>), deoxyribose (1456\u00a0cm<jats:sup>\u22121<\/jats:sup>) and collagen (1445, 1665\u00a0cm<jats:sup>\u22121<\/jats:sup>) were associated with normal and OAC tissue differences. Phenylalanine (1003\u00a0cm<jats:sup>\u22121<\/jats:sup>), proline\/collagen (1066, 1445\u00a0cm<jats:sup>\u22121<\/jats:sup>), phospholipids (1130\u00a0cm<jats:sup>\u22121<\/jats:sup>), CH<jats:sub>2<\/jats:sub> angular deformation (1295\u00a0cm<jats:sup>\u22121<\/jats:sup>), disaccharides (1462\u00a0cm<jats:sup>\u22121<\/jats:sup>) and proteins (amide I, 1672\/5\u00a0cm<jats:sup>\u22121<\/jats:sup>) were associated with Barrett\u2019s oesophagus and OAC tissue differences. These findings show the potential of using Raman microspectroscopy imaging for fast and accurate diagnoses of oesophageal pathologies and establishing subtle molecular changes predisposing to adenocarcinoma in a clinical setting.<\/jats:p>","DOI":"10.1007\/s00216-020-02637-1","type":"journal-article","created":{"date-parts":[[2020,4,25]],"date-time":"2020-04-25T00:02:30Z","timestamp":1587772950000},"page":"4077-4087","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Establishing spectrochemical changes in the natural history of oesophageal adenocarcinoma from tissue Raman mapping analysis"],"prefix":"10.1007","volume":"412","author":[{"given":"Ishaan","family":"Maitra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camilo L. 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