Diagnosis and Staging of Diffuse Large B-cell Lymphoma Using Label-free Surface-enhanced Raman Spectroscopy

Non-invasive diagnosis and staging of diffuse large B-cell lymphoma (DLBCL) were achieved using label-free surface-enhanced Raman spectroscopy (SERS). SERS spectra were measured for serum samples of DLBCL patients at different progressive stages and healthy controls (HCs), using colloidal silver nano-particles (AgNPs) as the substrate. Differences in the spectral intensities of Raman peaks were observed between the DLBCL and HC groups, and a close correlation between the spectral intensities of Raman peaks with the progressive stages of the cancer was obtained, demonstrating the possibility of diagnosis and staging of the disease using the serum SERS spectra. Multivariate analysis methods, including principal component analysis (PCA), linear discriminant analysis (LDA), support vector machine (SVM) classifier, and k-nearest neighbors (kNN) classifier, were used to build the diagnosis and staging models for DLBCL. Leave-one-out cross-validation was used to evaluate the performances of the models. The kNN model achieved the best performances for both diagnosis and staging of DLBCL: for the diagnosis analysis, the accuracy, sensitivity, and specificity were 87.3%, 0.921, and 0.809, respectively; for the staging analysis between the early (Stage I & II) and the late (Stage III & IV) stages, the accuracy was 90.6%, and the sensitivity values for the early and the late stages were 0.947 and 0.800, respectively. The label-free serum SERS in combination with multivariate analysis could serve as a potential technique for non-invasive diagnosis and staging of DLBCL.