Intact glycopeptides identified by LC-MS/MS as biomarkers for response to chemotherapy of locally advanced cervical cancer

Abstract

ObjectiveFor locally advanced cervical cancer (LACC), patients who respond to chemotherapy have a potential survival advantage compared to nonresponsive patients. Thus, it is necessary to explore specific biological markers for the efficacy of chemotherapy, which is beneficial to personalized treatment.MethodsIn the present study, we performed a comprehensive screening of site-specific N-glycopeptides in serum glycoproteins to identify glycopeptide markers for predicting the efficacy of chemotherapy, which is beneficial to personalized treatment. In total, 20 serum samples before and after neoadjuvant chemotherapy (NACT) from 10 LACC patients (NACT response, n=6) and NACT nonresponse, n=4) cases) were analyzed using LC-MS/MS, and 20 sets of mass spectrometry (MS) data were collected using liquid chromatography coupled with high-energy collisional dissociation tandem MS (LC-HCD-MS/MS) for quantitative analysis on the novel software platform, Byos. We also identified differential glycopeptides before and after chemotherapy in chemo-sensitive and chemo-resistant patients.ResultsIn the present study, a total of 148 glycoproteins, 496 glycosylation sites and 2279 complete glycopeptides were identified in serum samples of LACC patients. Before and after chemotherapy, there were 13 differentially expressed glycoproteins, 654 differentially expressed glycopeptides and 93 differentially expressed glycosites in the NACT responsive group, whereas there were 18 differentially expressed glycoproteins, 569 differentially expressed glycopeptides and 99 differentially expressed glycosites in the NACT nonresponsive group. After quantitative analysis, 6 of 570 glycopeptides were identified as biomarkers for predicting the sensitivity of neoadjuvant chemotherapy in LACC. The corresponding glycopeptides included MASP1, LUM, ATRN, CO8A, CO8B and CO6. The relative abundances of the six glycopeptides, including MASP1, LUM, ATRN, CO8A, CO8B and CO6, were significantly higher in the NACT-responsive group and were significantly decreased after chemotherapy. High levels of these six glycopeptides may indicate that chemotherapy is effective. Thus, these glycopeptides are expected to serve as biomarkers for predicting the efficacy of neoadjuvant chemotherapy in locally advanced cervical cancer.ConclusionThe present study revealed that the N-glycopeptide of MASP1, LUM, ATRN, CO8A, CO8B and CO6 may be potential biomarkers for predicting the efficacy of chemotherapy for cervical cancer.

Unveiling diagnostic and therapeutic strategies for cervical cancer: biomarker discovery through proteomics approaches and exploring the role of cervical cancer stem cells

“…Li et al. ( 80 ) have recently demonstrated a study to identify glycopeptide markers in serum glycoproteins that can predict the efficacy of chemotherapy for locally advanced cervical cancer (LACC), thus enabling personalized treatment. They conducted a comprehensive screening of site-specific N-glycopeptides in serum samples from LACC patients before and after neoadjuvant chemotherapy (NACT).…”

“…High levels of these glycopeptides indicated chemotherapy effectiveness. The authors suggested that theses six N-glycopeptides may serve as potential biomarkers for predicting the efficacy of chemotherapy in cervical cancer ( 80 ).…”

Shape complementarity processes for ultrashort-burst sensitive M13–PEG–WS2-powered MCF-7 cancer cell sensors

“…4–6 In the case of cancer, it is beneficial to discover biomarkers of the inflammatory process in addition to the qualitative and quantitative identification of cancer-specific biomarkers. 7–11 According to Brenner et al , these biomarkers include acute-phase proteins, reactive oxygen and nitrogen species, immune-related effectors, cytokines or chemokines, mediators and prostaglandins, and cyclooxygenase-related factors. 12 The cancer cell type is a promising contender for next-generation biomarkers for applications in surveying treatment responses or unfavourable cases, diagnosis and toxicology.…”