RESUMO
Background: Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed. Objective and design: This retrospective multi-center plasma proteomics study was performed to identify potential blood-based biomarkers in 36 CRC patients and 26 healthy volunteers by high-resolution mass spectrometry proteomics followed by the validation in an independent CRC cohort (60 CRC patients and 44 healthy subjects) of identified selected biomarkers. Results: Among the 322 identified plasma proteins, 37 were changed between CRC patients and healthy volunteers and were associated with the complement cascade, cholesterol metabolism, and SERPIN family members. Increased levels in CRC patients of the complement proteins C1QB, C4B, and C5 as well as pro-inflammatory proteins, lipopolysaccharide-binding protein (LBP) and serum amyloid A4, constitutive (SAA4) were revealed for first time. Importantly, increased level of C5 was verified in an independent validation CRC cohort. Increased C4B and C8A levels were correlated with cancer-associated inflammation and CRC progression, while cancer-associated inflammation was linked to the acute-phase reactant leucine-rich alpha-2-glycoprotein 1 (LRG1) and ceruloplasmin. Moreover, a 4-protein signature including C4B, C8A, apolipoprotein C2 (APO) C2, and immunoglobulin heavy constant gamma 2 was changed between early and late CRC stages. Conclusion: Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care.
RESUMO
Despite great scientific efforts, deep understanding of coronavirus-19 disease (COVID-19) immunopathology and clinical biomarkers remains a challenge. Pre-existing comorbidities increase the mortality rate and aggravate the exacerbated immune response against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, which can result in more severe symptoms as well as long-COVID and post-COVID complications. In this study, we applied proteomics analysis of plasma samples from 28 patients with SARS-CoV-2, with and without pre-existing comorbidities, as well as their corresponding controls to determine the systemic protein changes caused by the SARS-CoV-2 infection. As a result, the protein signature shared amongst COVID-19 patients with comorbidities was revealed to be characterized by alterations in the coagulation and complement pathways, acute-phase response proteins, tissue damage and remodeling, as well as cholesterol metabolism. These altered proteins may play a relevant role in COVID-19 pathophysiology. Moreover, several novel potential biomarkers for early diagnosis of the SARS-CoV-2 infection were detected, such as increased levels of keratin K22E, extracellular matrix protein-1 (ECM1), and acute-phase response protein α-2-antiplasmin (A2AP). Importantly, elevated A2AP may contribute to persistent clotting complications associated with the long-COVID syndrome in patients with comorbidities. This study provides new insights into COVID-19 pathogenesis and proposes novel potential biomarkers for early diagnosis that could be facilitated for clinical application by further validation studies.