Verification of potential protein biomarkers for detection of endometrial cancer by targeted mass spectrometry

Date

2025-8-19

Author

Yıldırım, Öykü Su

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Endometrial cancer (EC) is one of the most common gynecologic malignancies, with 420.242 new cases and 97.704 deaths reported worldwide in 2022. EC comprises two major subtypes, endometrioid (EEC) and non-endometrioid (NEC), which differ in prognosis and therapeutic response. Thus, subtype-specific biomarkers are crucial for precise diagnosis, prognosis, and treatment stratification. This study aims to verify previously reported potential biomarkers for EC as an essential phase in the biomarker development pipeline and to evaluate their potential diagnostic and prognostic value. For this purpose, multiple-reaction-monitoring (MRM) method specific to nine proteins, namely transgelin (Q01995), peptidyl prolyl cis-transisomerase (Q00688), cyclophilin A (P62937), macrophage capping protein (P40121), pyruvate kinase M1/M2 (P14618), glutathione S-transferase P (P09211), manganese-superoxide dismutase (P04179), cytosol aminopeptidase (P28838), and complement component C4A (P0C0L4), was developed with stable isotopic-labeled (SIL) peptides. Method performance was evaluated through linearity, limit-of-detection, instrument stability, and reprodubility of sample preparation by following European Medicines Agency guideline. Unique peptides of nine proteins were monitored in tissue samples from EEC, NEC, and healthy groups following protein extraction and proteolytic digestion. Seven proteins displayed significant dysregulation. Down-regulation of Q01995 is a recurring event in malignancies, serving as a potential biomarker of cancer progression. Conversely, P14618, P40121, Q00688, P28838 were up-regulated, reflecting hallmarks of cancer. However, down-regulation of P0C0L4 and up-regulation of P09211 are not typically observed across cancers. Importantly, P09211 was the only protein showing subtype-specific elevation in EEC compared to NEC, highlighting its prognostic value. Further studies are needed for the verified proteins to be translated into clinical practice.

Subject Keywords

Biomarker, Endometrial cancer, Mass spectrometry, Multiple reaction monitoring (MRM), Targeted proteomics

URI

https://hdl.handle.net/11511/115684

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Graduate School of Natural and Applied Sciences, Thesis