Rationale: The identification and evaluation of novel biomarkers are essential to clinical diagnosis and prognosis of colorectal cancer (CRC). Serum phosphopeptides have been recognized as a potential signature pool for cancers; therefore, we aim to profile the expression of serum phosphopeptides and to evaluate their feasibility in CRC diagnosis.
Methods: We conducted the characterization and absolute quantification of endogenous phosphopeptides in sera using liquid chromatography-mass spectrometry analysis in combination with enrichment of phosphopeptides by ZrAs-Fe3 O4 @SiO2 nanoparticles and use of deuterium-labeled standards. Differentially expressed analysis of four phosphopeptides was performed, generating a two-phosphopeptide-based biomarker, LF3-4 , by logistic regression analysis, where LF3-4 is equal to (5.85 - 5.13 × [F3] - 3.57 × [F4]), and [F3] and [F4] are the concentration of phosphopeptides DpSGEGDFLAEGGGVR and ADpSGEGDFLAEGGGVR in sera, respectively.
Results: The LF3-4 values showed significant difference in CRC cases compared with controls, and yielded a specificity of 100%, leading to correct classification of 56 (93%) out of 60 CRC patients, including 12 (92.3%) of 13 CRC cases in stage I. Double-blind validation showed that 97.5% of CRC cases were discriminated accurately.
Conclusions: The LF3-4 value was firstly verified to be a potential biomarker for CRC diagnosis, and may expand our view in underlying mechanisms for CRC.
© 2022 John Wiley & Sons Ltd.