A comparative analysis of different biofluids towards ovarian cancer diagnosis using Raman microspectroscopy

Panagiotis Giamougiannis,Nicholas J Wood,Camilo L M Morais,Rita Grabowska,Katherine M Ashton,Pierre L Martin-Hirsch,Francis L Martin

doi:10.1007/s00216-020-03045-1

Panagiotis Giamougiannis, Nicholas J Wood + Show 5 more

Open Access

https://doi.org/10.1007/s00216-020-03045-1

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Abstract

Biofluids, such as blood plasma or serum, are currently being evaluated for cancer detection using vibrational spectroscopy. These fluids contain information of key biomolecules, such as proteins, lipids, carbohydrates and nucleic acids, that comprise spectrochemical patterns to differentiate samples. Raman is a water-free and practically non-destructive vibrational spectroscopy technique, capable of recording spectrochemical fingerprints of biofluids with minimum or no sample preparation. Herein, we compare the performance of these two common biofluids (blood plasma and serum) together with ascitic fluid, towards ovarian cancer detection using Raman microspectroscopy. Samples from thirty-eight patients were analysed (n = 18 ovarian cancer patients, n = 20 benign controls) through different spectral pre-processing and discriminant analysis techniques. Ascitic fluid provided the best class separation in both unsupervised and supervised discrimination approaches, where classification accuracies, sensitivities and specificities above 80% were obtained, in comparison to 60–73% with plasma or serum. Ascitic fluid appears to be rich in collagen information responsible for distinguishing ovarian cancer samples, where collagen-signalling bands at 1004 cm−1 (phenylalanine), 1334 cm−1 (CH3CH2 wagging vibration), 1448 cm−1 (CH2 deformation) and 1657 cm−1 (Amide I) exhibited high statistical significance for class differentiation (P < 0.001). The efficacy of vibrational spectroscopy, in particular Raman spectroscopy, combined with ascitic fluid analysis, suggests a potential diagnostic method for ovarian cancer.Graphical abstractRaman microspectroscopy analysis of ascitic fluid allows for discrimination of patients with benign gynaecological conditions or ovarian cancer.

Highlights

Ovarian cancer is the seventh most commonly occurring cancer in women worldwide, with nearly 300,000 new cases diagnosed in 2018 [1]
Three different pre-processing approaches were applied to the raw dataset: the first (Baseline + Norm.) being SG smoothing followed by automatic weighted least squares (AWLS) baseline correction and vector normalisation, which removes random noise, corrects the baseline and different sample thickness and concentrations; the second (EMSC + Baseline) was SG smoothing followed by extended multiplicative scatter correction (EMSC) and AWLS baseline correction, which has an effect similar to the previous pre-processing, but it corrects for light scattering and does not correct for samples with different concentrations; and the third approach (1st derivative) was SG smoothing followed by 1st derivative, which corrects for random noise, baseline, sample thickness and light scattering, but increases substantially the noise level [26]
The principal component analysis (PCA) score plots for the three types of pre-processed data are shown in Fig. 2, where P-values were calculated based on the threedimensional score plot by using a MANOVA test with the score values on PC1, PC2 and PC3

Summary

Introduction

Ovarian cancer is the seventh most commonly occurring cancer in women worldwide, with nearly 300,000 new cases diagnosed in 2018 [1]. In the UK, it is the sixth most common cancer in women, with around 7400 new diagnoses every year. It is a leading cause of mortality from gynaecological malignancies, accounting for 5% of all cancer. This is because its presentation is notoriously non-specific with symptoms that are widely experienced among the general population; most women tend to present with advanced disease [3]. A common feature of women with ovarian cancer is the presence of ascites (accumulation of free fluid in the peritoneal cavity). In cases of disseminated intra-abdominal cancer (such as ovarian cancer), exaggerated production of peritoneal fluid is induced due to increased leakiness of tumour microvasculature and obstruction of lymphatic vessels [5]. More than one-third of ovarian cancer patients present with significant ascites at diagnosis [6]

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