Detection of ovarian cancer (\xb1 neo-adjuvant chemotherapy effects) via ATR-FTIR spectroscopy: comparative analysis of blood and urine biofluids in a large patient cohort

Panagiotis Giamougiannis,Camilo L M Morais,Brice Rodriguez,Francis L Martin,Nicholas J Wood,Pierre L Martin-Hirsch

doi:10.1007/s00216-021-03472-8

Abstract

Ovarian cancer remains the most lethal gynaecological malignancy, as its timely detection at early stages remains elusive. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy of biofluids has been previously applied in pilot studies for ovarian cancer diagnosis, with promising results. Herein, these initial findings were further investigated by application of ATR-FTIR spectroscopy in a large patient cohort. Spectra were obtained by measurements of blood plasma and serum, as well as urine, from 116 patients with ovarian cancer and 307 patients with benign gynaecological conditions. A preliminary chemometric analysis revealed significant spectral differences in ovarian cancer patients without previous chemotherapy (n = 71) and those who had received neo-adjuvant chemotherapy—NACT (n = 45), so these groups were compared separately with benign controls. Classification algorithms with blind predictive model validation demonstrated that serum was the best biofluid, achieving 76% sensitivity and 98% specificity for ovarian cancer detection, whereas urine exhibited poor performance. A drop in sensitivities for the NACT ovarian cancer group in plasma and serum indicates the potential of ATR-FTIR spectroscopy to identify chemotherapy-related spectral changes. Comparisons of regression coefficient plots for identification of biomarkers suggest that glycoproteins (such as CA125) are the main classifiers for ovarian cancer detection and responsible for smaller differences in spectra between NACT patients and benign controls. This study confirms the capacity of biofluids’ ATR-FTIR spectroscopy (mainly blood serum) to diagnose ovarian cancer with high accuracy and demonstrates its potential in monitoring response to chemotherapy, which is reported for the first time.Graphical abstractATR-FTIR spectroscopy of blood serum achieves good segregation of ovarian cancers from benign controls, with attenuation of differences following neo-adjuvant chemotherapy.

Highlights

Ovarian cancer is the 8th most common cancer-related cause of death in women internationally, with incidence and mortality projected to increase markedly in the 20 years [1, 2]
In cases where upfront operating is deemed unlikely to achieve complete cytoreduction, chemotherapy is initiated first followed by interval debulking surgery (IDS) and subsequent administration of further chemotherapy cycles [4, 5]
Serum CA125 levels were measured for all patients at the time of their attendance for surgery and for ovarian cancer patients who received NACT at the time of their disease diagnosis as well

Summary

Introduction

Ovarian cancer is the 8th most common cancer-related cause of death in women internationally, with incidence and mortality projected to increase markedly in the 20 years [1, 2]. ATR-FTIR spectroscopy was used to identify the potential of plasma, serum and urine in a large prospective study for the detection of ovarian cancer.

Results

Conclusion