Establishing spectrochemical changes in the natural history of oesophageal adenocarcinoma from tissue Raman mapping analysis

Ishaan Maitra,Katherine M Ashton,Kássio M G Lima,Ravindra S Date,Francis L Martin,Camilo L M Morais,Danielle Bury

doi:10.1007/s00216-020-02637-1

Abstract

Raman spectroscopy is a fast and sensitive technique able to identify molecular changes in biological specimens. Herein, we report on three cases where Raman microspectroscopy was used to distinguish normal vs. oesophageal adenocarcinoma (OAC) (case 1) and Barrett’s 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’s oesophagus vs. OAC tissues were discriminated with accuracies ranging from 98 to 100% (97–100% 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–O–C skeletal mode in β-glucose (900 cm−1), lipids (967 cm−1), phosphodioxy (1296 cm−1), deoxyribose (1456 cm−1) and collagen (1445, 1665 cm−1) were associated with normal and OAC tissue differences. Phenylalanine (1003 cm−1), proline/collagen (1066, 1445 cm−1), phospholipids (1130 cm−1), CH2 angular deformation (1295 cm−1), disaccharides (1462 cm−1) and proteins (amide I, 1672/5 cm−1) were associated with Barrett’s 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.Graphical abstractGraphical abstract demonstrating how oesophageal tissue is processed through Raman mapping analysis in order to detect spectral differences between stages of oesophageal transformation to adenocarcinoma

Highlights

Oesophageal adenocarcinoma (OAC) is an aggressive disease which usually presents de novo and late with a poor prognosis
There is a proven association between adenocarcinoma and Barrett’s oesophagus, a condition that appears to arise in response to chronic inflammation from gastro-oesophageal reflux disease (GORD) [2, 3]
The average raw and pre-processed (Savitzky–Golay smoothing and automatic weighted least squares (AWLS) baseline correction) Raman spectra for normal and OAC tissue are depicted in Fig. 2 a and b, respectively

Summary

Introduction

Oesophageal adenocarcinoma (OAC) is an aggressive disease which usually presents de novo and late with a poor prognosis. In the UK, the overall OAC 5-year survival rate is as low as 19% [1]. It is uncertain if alcohol and smoking contribute to the development of OAC. There is a proven association between adenocarcinoma and Barrett’s oesophagus, a condition that appears to arise in response to chronic inflammation from gastro-oesophageal reflux disease (GORD) [2, 3]. If dysplasia can initially be diagnosed accurately with adjuncts to histology, this would benefit earlier treatment and prevent the burden of patients developing OAC

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Discussion

Conclusion