Surface-enhanced Raman spectroscopy of serum accurately detects prostate cancer in patients with prostate-specific antigen levels of 4-10 ng/mL

Abstract

The surface-enhanced Raman spectroscopy (SERS) of blood serum was investigated to differentiate between prostate cancer (PCa) and benign prostatic hyperplasia (BPH) in males with a prostate-specific antigen level of 4-10 ng/mL, so as to reduce unnecessary biopsies. A total of 240 SERS spectra from blood serum were acquired from 40 PCa subjects and 40 BPH subjects who had all received prostate biopsies and were given a pathological diagnosis. Multivariate statistical techniques, including principal component analysis (PCA) and linear discriminant analysis (LDA) diagnostic algorithms, were used to analyze the spectra data of serum from patients in control (CTR), PCa and BPH groups; results offered a sensitivity of 97.5%, a specificity of 100.0%, a precision of 100.0% and an accuracy of 99.2% for CTR; a sensitivity of 90.0%, a specificity of 97.5%, a precision of 94.7% and an accuracy of 98.3% for BPH; a sensitivity of 95.0%, a specificity of 93.8%, a precision of 88.4% and an accuracy of 94.2% for PCa. Similarly, this technique can significantly differentiate low- and high-risk PCa with an accuracy of 92.3%, a specificity of 95% and a sensitivity of 89.5%. The results suggest that analyzing blood serum using SERS combined with PCA-LDA diagnostic algorithms is a promising clinical tool for PCa diagnosis and assessment.

Keywords: Ag nanoparticles; benign prostatic hyperplasia; gray zone; linear discriminant analysis; principle component analysis; spectral classification.

Figure 1

The SEM image of AgNPs (scale =100 nm). Abbreviations: SEM, scanning electron microscope; AgNP, silver nanoparticle.

Figure 2

SERS spectra of CTR (green), BPH (blue), and PCa (red) groups. Note: Solid lines indicate the mean spectra, and shades around them mean their standard errors. Abbreviations: SERS, surface-enhanced Raman spectroscopy; CTR, control; BPH, benign prostatic hyperplasia; PCa, prostate cancer; au, atomic unit.

Figure 3

Scatter plot of the scores of the linear discriminant, describing the separation between the SERS spectra of the PCa group, BPH group and CTR group achieved by the PCA–LDA model. Abbreviations: SERS, surface-enhanced Raman spectroscopy; PCa, prostate cancer; BPH, benign prostatic hyperplasia; CTR, control; PCA, principal component analysis; LDA, linear discriminant analysis.

Figure 4

Scatter plot of the scores of the linear discriminant, describing the separation between the SERS spectra of the LG group and the HG group achieved by the PCA–LDA model. Abbreviations: SERS, surface-enhanced Raman spectroscopy; LG, low grade; HG, high grade; PCA, principal component analysis; LDA, linear discriminant analysis.

Figure 5

ROC curve of discrimination results for serum SERS spectra out of the PCA–LDA-based spectral classification with discrimination scores. Note: The integration of AUC for LG versus HG is 0.966. Abbreviations: ROC, receiver operating characteristic; SERS, surface-enhanced Raman spectroscopy; PCA, principal component analysis; LDA, linear discriminant analysis; AUC, area under the ROC curve; LG, low grade; HG, high grade.