结直肠癌(CRC)的预后取决于疾病阶段,晚期生存率较低。目前的CRC筛查方案主要采用结肠镜检查,受限于其侵入性和高成本。因此,非侵入性,成本效益高,迫切需要准确的替代方案。
■这项回顾性多中心血浆蛋白质组学研究通过高分辨率质谱蛋白质组学,然后在独立的CRC队列(60名CRC患者和44名健康受试者)中验证鉴定的选定生物标志物,以鉴定36名CRC患者和26名健康志愿者中潜在的基于血液的生物标志物。
■在322个鉴定的血浆蛋白中,37例CRC患者和健康志愿者之间发生了变化,并且与补体级联反应有关,胆固醇代谢,和SERPIN家族成员。CRC患者的补体蛋白C1QB水平升高,C4B,和C5以及促炎蛋白,首次发现脂多糖结合蛋白(LBP)和血清淀粉样蛋白A4组成型(SAA4)。重要的是,C5水平升高在独立验证CRC队列中得到证实.C4B和C8A水平升高与癌症相关的炎症和CRC进展相关。而癌症相关的炎症与急性期反应物富含亮氨酸的α-2-糖蛋白1(LRG1)和铜蓝蛋白有关。此外,包括C4B的4-蛋白质签名,C8A,载脂蛋白C2(APO)C2和免疫球蛋白重常数γ2在早期和晚期CRC阶段之间发生了变化。
■我们的结果表明C5可能是CRC诊断的潜在生物标志物。进一步的验证研究将有助于这些新的潜在生物标志物的应用,以改善CRC诊断和患者护理。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.