Mass Spectrometry Proteomics Characterization of Plasma Biomarkers for Colorectal Cancer Associated With Inflammation

与炎症相关的结肠直肠癌血浆生物标志物的质谱蛋白质组学表征

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作者:Víctor Urbiola-Salvador, Agnieszka Jabłońska, Dominika Miroszewska, Weronika Kamysz, Katarzyna Duzowska, Kinga Drężek-Chyła, Ronny Baber, René Thieme, Ines Gockel, Marek Zdrenka, Ewa Śrutek, Łukasz Szylberg, Michał Jankowski, Dariusz Bała, Wojciech Zegarski, Tomasz Nowikiewicz, Wojciech Makarewicz, 

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.

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.

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.

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