CD5 molecule-like and transthyretin as putative biomarkers of chronic myeloid leukemia - an insight from the proteomic analysis of human plasma

Abstract

Better and sensitive biomarkers are needed to help understand the mechanism of disease onset, progression, prognosis and monitoring of the therapeutic response. Aim of this study was to identify the candidate circulating markers of chronic-phase chronic myeloid leukemia (CP-CML) manifestations, having potential to develop into predictive- or monitoring-biomarkers. A proteomic approach, two-dimensional gel electrophoresis in conjunction with mass spectrometry (2DE-MS), was employed for this purpose. Based on the spot intensity measurements, six proteins were found to be consistently dysregulated in CP-CML subjects compared to the healthy controls [false discovery rate (FDR) threshold ≤0.05]. These were identified as α-1-antichymotrypsin, α-1-antitrypsin, CD5 molecule-like, stress-induced phosphoprotein 1, vitamin D binding protein isoform 1 and transthyretin by MS analysis [PMF score ≥79; data accessible via ProteomeXchange with identifier PXD002757]. Quantitative ELISA, used for validation of candidate proteins both in the pre-treated and nilotinib-treated CP-CML cases, demonstrate that CD5 molecule-like, transthyretin and alpha-1-antitrypsin may serve as useful predictive markers and aid in monitoring the response of TKI-based therapy (ANOVA p < 0.0001). Two of the circulating marker proteins, identified in this study, had not previously been associated with chronic- or acute-phase myeloid leukemia. Exploration of their probable association with CP-CML, in a larger study cohort, may add to our understanding of the disease mechanism besides developing clinically useful biomarkers in future.

Identification of potential cervical cancer serum biomarkers in Thai patients

“…TTR has been previously used in nutritional indexes, due to the association between its plasma levels and the nutritional supply. TTR levels were identified to be decreased in the sera of various cancer types, such as lung, prostate, gastric, ovarian, pancreatic cancer, cholangiocarcinoma and chronic myeloid leukemia (30)(31)(32)(33)(34)(35)(36); therefore, TTR may be considered a potential biomarker. Consistent with these studies, the results from the present study indicated significantly decreased TTR levels in the sera of patients with advanced-stage cervical cancer, compared with the HPV negative normal controls and patients with early-stage cervical cancer.…”

“…Consistent with these studies, the results from the present study indicated significantly decreased TTR levels in the sera of patients with advanced-stage cervical cancer, compared with the HPV negative normal controls and patients with early-stage cervical cancer. In addition, the TTR levels demonstrated an inverse correlation with tumor volume in gastric and ovarian cancer (32,37), were associated with prostate cancer stage (31) and serve as a therapy-associated biomarker in patients with chronic myeloid leukemia (36). It has been well established that the liver increases the production of positive acute phase reactants and decreases the production of negative acute phase reactants in response to insults, including trauma in the body, inflammation, infection and malignancy.…”

Upregulated Expression of Calcium‐Dependent Annexin A6: A Potential Biomarker of Ovarian Carcinoma

“…The gel pellets showing differentially stained spots in the 2D gels of the control and the tumor samples were excised and the proteins in them were digested with sequencing grade trypsin (Promega, Southampton, UK) as described earlier with slight modifications. The digested peptides extract was analyzed by MALDI‐TOF MS (Ultraflex III, Bruker Daltonics, Germany).…”

“…More specifically, identification of proteins differentially represented in OC tissues compared to normal ovarian tissues can provide potential diagnostic, prognostic, and therapeutic biomarkers and thus, may facilitate in deciding the available treatment choice(s) . Amongst the various proteomic approaches used for biomarker identification, 2D gel electrophoresis (2‐DE) followed by mass spectrometric (MS) identification of the differentially regulated molecules, has customarily been utilized in numerous malignancies …”

Clinical and laboratory features of ALS

“…CD5L also acts to downregulate the pathogenicity of Th17 cells [303] . CD5L has been studied as a biomarker and is elevated in serum in chronic leukemia [304] .…”