Identification of serum peptide biomarkers for predicting the efficacy of first-line chemotherapy in advanced epithelial ovarian cancer by MALDI-TOF-MS with magnetic bead technology.

Abstract

Abstract Objective This study explored serum protein biomarkers for predicting the efficacy of first-line chemotherapy in advanced epithelial ovarian cancer using MALDI-TOF-MS combined with magnetic bead technology. Methods A total of 182 epithelial ovarian cancer patients were admitted to the Department of Gynaecologic Oncology, Cancer Hospital of the Chinese Academy of Medical Sciences between March 2018 and September 2018. Sixty-four of these patients had stage III/IV disease and received neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) and adjuvant chemotherapy (mucinous and low-grade serous carcinoma were excluded). Serum samples were collected before treatment. After a median follow-up time of 16 months, 25 chemosensitive patients with progression-free survival (PFS) >12 months and 10 chemoresistant patients <6 months after adjuvant chemotherapy were selected as the research subjects. Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) was used for peptide profiling of the serum samples to compare significantly differentially expressed peptides between the chemosensitive group and chemoresistant group (score >5), and peptide peaks with AUC ≥ 0.8 were identified. Liquid chromatography–mass spectrometry (LC‒MS/MS) was further used to determine the composition of the differentially expressed peptides. Results In the range of 1000-10000 m/z, 71 differential peptide peaks between the chemoresistant and chemosensitive groups were initially detected. ROC curve analysis showed that among the 71 differential protein peaks, there were 22 differential polypeptide peaks with an AUC ≥0.8, of which 10 were highly expressed in the chemoresistant group and 12 were highly expressed in the chemosensitive group. LC‒MS/MS analysis identified the protein components of 4 polypeptide peaks among the 10 differentially expressed polypeptide peaks in the chemoresistant group: 4634.22 m/z as fragments of serum amyloid A-1, 1287.56 m/zas fragments of prothrombin, and 1099.56 m/z and 2018.39 m/z as fragments of complement C3; the sensitivity and specificity of these three proteins for predicting first-line chemotherapeutic efficacy were 100%, 100%, and 96% and 80%, 100%, and 100%, respectively. No protein component was identified among the 12 differential protein peaks in the chemosensitive group. Conclusion Serum amyloid A-1, prothrombin and complement C3 were highly expressed in chemoresistant patients; thus, they might be related to the poor efficacy of paclitaxel/carboplatin first-line chemotherapy in advanced ovarian cancer. It is necessary to further explore their predictive value.