UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia.
Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia.
Cytokine. 2017 Nov;99:35-42. doi: 10.1016/j.cyto.2017.06.015. Epub 2017 Jul 6.
Soluble proteins including cytokines, chemokines and growth factors are small proteins that mediate and regulate immunity. They involved in the pathogenesis of many diseases including cancers. The concentration of these proteins in biological fluids (serum or plasma) and tissues in diseases may suggest pathway activation that leads to inflammatory response or disease progression. Therefore, these soluble proteins may be useful as a tool for screening, diagnosis classification between stages of disease or surveillance for therapy. Enzyme-linked immunosorbent assays (ELISA) and bioassay have been used as a gold standard in cytokine level measurements in clinical practice. However, these methods allow only single cytokine detection at a time and ineffective for screening purposes. Hence, the innovation of multiplexing technology allows measurement of many these soluble proteins simultaneously, thus allowing rapid, cost effective and better efficiency by using a minute amount of sample. In this study, we explored the profiles of key inflammatory cytokines, chemokines and other soluble proteins from the serum derived from colorectal carcinoma (CRC, n=20), colorectal polyps (P, n=20) and healthy volunteers (N, n=20) using multiplexed bead-based immunoassays. We aimed to evaluate if the levels of these soluble proteins can classify these groups of populations and explore the possible application of the soluble proteins as biomarkers in early stage screening and/or surveillance. We observed significant high IL-4, MIP-1β, FasL and TGF-β1 levels but lower levels for RANTES in P-derived serum as compared to N-derived serum. Significant high IL-8, VEGF, MIP-1β, Eotaxin and G-CSF observed in CRC-derived serum when compared to N-derived serum. Between CRC- and P-derived serum, significantly higher levels of IL-8, Eotaxin and G-CSF but lower levels for TGF-β1 were detected in CRC-derived serum. These preliminary results were obtained from small sample size and could be further validated with larger sample size cohort to produce a panel of biomarkers for CRC and P patients. Our findings might be useful in developing a disease-specific panel for biomarker screening assay. This could be used for early diagnosis and/or treatment surveillance.
可溶性蛋白包括细胞因子、趋化因子和生长因子等,是介导和调节免疫的小蛋白。它们参与了许多疾病的发病机制,包括癌症。这些蛋白质在生物体液(血清或血浆)和组织中的浓度在疾病中可能提示途径激活,导致炎症反应或疾病进展。因此,这些可溶性蛋白可用作筛选、诊断、疾病分期分类或治疗监测的工具。酶联免疫吸附测定(ELISA)和生物测定已被用作临床实践中细胞因子水平测量的金标准。然而,这些方法一次只能检测一种细胞因子,不适合用于筛选。因此,多重技术的创新允许同时测量许多这些可溶性蛋白,从而使用少量样本实现快速、经济高效和更好的效率。在这项研究中,我们使用基于珠的多重免疫分析方法探索了来自结直肠癌(CRC,n=20)、结直肠息肉(P,n=20)和健康志愿者(N,n=20)血清中的关键炎症细胞因子、趋化因子和其他可溶性蛋白的图谱。我们旨在评估这些可溶性蛋白的水平是否可以对这些人群进行分类,并探讨这些可溶性蛋白作为早期筛查和/或监测生物标志物的可能应用。我们观察到 P 来源的血清中 IL-4、MIP-1β、FasL 和 TGF-β1 水平显著升高,而 RANTES 水平较低,N 来源的血清中则相反。与 N 来源的血清相比,CRC 来源的血清中观察到显著高水平的 IL-8、VEGF、MIP-1β、Eotaxin 和 G-CSF。与 P 来源的血清相比,CRC 来源的血清中检测到更高水平的 IL-8、Eotaxin 和 G-CSF,而 TGF-β1 水平较低。这些初步结果来自于小样本量,可以进一步用更大的样本量队列进行验证,以产生 CRC 和 P 患者的生物标志物组合。我们的发现可能有助于开发用于生物标志物筛选测定的疾病特异性面板。这可用于早期诊断和/或治疗监测。