Background: Post treatment minimal residual disease (MRD) determination contributes to impending relapse prediction, chemotherapy response and clinical outcomes assessment, guiding clinicians to develop reasonable and effective individual chemotherapy options after induction/consolidation. This study was to identify serum candidate peptides for monitoring adult acute myeloid leukemia (AML) MRD.Results: 47 statistically different expressed peptide peaks were obtained in the molecular weight range of 700-10000 Da. Quick classifier (QC) model had optimal distinction efficiency, in the training set with a sensitivity of 90% and a specificity of 93.33%. Peptides were identified as ubiquitin-like modifier activating enzyme 1(UBA1), isoform 1 of fibrinogen alpha chain precursor and platelet factor 4(PF4). The peptide up-regulated in newly diagnosed AML patients were decreased to the normal level after CR. When refractory & relapsed, relative intensity was elevated again. Results were contrary to down-regulated peptide peaks. Western blot demonstrated that levels of the UBA1 protein did not differ between the leukemia and normal cells. Levels of isoform 1 of fibrinogen alpha chain precursor protein and PF4 protein were both decreased in leukemia cells comparing with normal cells. The serum levels of the PF4 in the newly diagnosed AML patients and healthy controls were significantly different. Further correlation analysis did not indicate the correlated relation between platelet counts and PF4 content, the correlation coefficient was 0.097. Kaplan–Meier analyses of overall survival showed that relative intensity of peptides was correlated with patient’s clinical outcome.Conclusions: We speculate the peptides can be used as potential markers for monitoring minimal residual disease and clinical outcome assessment.

There is an urgent need for the identification of new, clinically useful biomarkers of CRC to enhance diagnostic and prognostic capabilities. We performed proteomic profiling on serum samples from paired pre- and post-operative CRC patients, colorectal polyps patients and healthy controls using an approach combining magnetic bead-based weak cation exchange and matrix-assisted laser desorption ionization-time of flight mass spectrometry. We next performed liquid chromatography-electrospray ionization-tandem mass spectrometry to identify the proteins and selected potential biomarker based on bioinformatics analysis of the TCGA and GEO dataset. We examined SETD7 expression in serum and tissue samples by ELISA and immunohistochemistry respectively and explored the biological function of SETD7 in vitro. 85 differentially expressed peptides were identified. Five peptides showing the most significant changes in abundance across paired pre- and post-operation CRC patients, colorectal polyps patients and healthy controls were identified as peptide regions of FGA, MUC5AC and SETD7. Bioinformatics analysis suggested that the up-regulation of SETD7 in CRC is relatively specific. Validation studies showed that SETD7 expression increased from healthy controls to those with colorectal polyps and finally CRC patients, and decreased after surgery. The sensitivity and specificity of SETD7 were 92.17% and 81.08%, with a high diagnostic value (AUC = 0.9477). In addition, SETD7 expression was significantly correlated with tumor stage and microsatellite instability. Knockdown of SETD7 inhibited cancer cell proliferation, induced G1/S cell cycle arrest and increased apoptosis. Our data indicate that SETD7 could serve as a potential diagnostic and prognostic biomarker for CRC.

Liu H, et al. Allergy Asthma Immunol Res. 2023 Jul;15(4):473-495. https://doi.org/10.4168/aair.2023.15.4.473

The persistence of minimal residual disease (MRD) during therapy is the strongest adverse prognostic factor in acute lymphocytic leukemia (ALL). This study was to identify serum candidate peptides for monitoring MRD in adult ALL. A total of 33 peptides in the molecular weight range of 1000-10000 Da were detected using ClinProt system and statistically different between adult patients with ALL and healthy controls. Quick classifier (QC) algorithm was used to obtain a diagnostic model consisting of five peptides that could discriminate patients with ALL from controls with a high sensitivity (100%) and specificity (96.67%). The peptides in the QC model were identified as fibrinogen alpha chain (FGA), glutathione S-transferase P1 (GSTP1), isoform 1 of fibrinogen alpha chain precursor, platelet factor 4 (PF4) by high pressure/performance liquid chromatography mass spectrometry/mass spectrometry. Relative intensities of the five peptides were compared among ALL different groups for the potential importance of MRD evaluation in ALL. The peptides with increased relative intensities in newly diagnosed (ND) ALL patients were found to be decreased in their relative intensities after complete remission (CR) of adult ALL. When ALL patients were refractory & relapsed (RR), relative intensities of the peptides were elevated again. Peptides with decreased relative intensities in ND and RR ALL patients were found to be increased in their relative intensities when ALL patients achieved CR. The findings were validated by ELISA and western blot. Further linear regression analyses were performed to eliminate the influence of platelet and white blood cell counts on serum protein contents and indicated that there were no correlations between the contents of all four proteins (PF4, connective tissue active peptide III, FGA and GSTP1) and white blood cell or platelet counts in ALL different groups and healthy control. We speculate the five peptides, FGA, isoform 1 of fibrinogen alpha chain precursor, GSTP1, PF4 and connective tissue active peptide III would be potential biomarkers for forecasting relapse, monitoring MRD and evaluating therapeutic response in adult ALL.