Department of Biochemistry, Genetics and Immunology, Faculty of Biology, University of Vigo, As Lagoas-Marcosende s/n. 36310 Vigo, Spain.
Health Care Unit, Complutense University of Madrid, Spain.
Dis Markers. 2020 Jan 21;2020:4347936. doi: 10.1155/2020/4347936. eCollection 2020.
Current screening trials are showing reduction in colorectal cancer incidence and mortality. However, participation rates are often low, and blood-based tests could complement existing screening strategies. CD26 protein (sCD26) and its dipeptidyl peptidase IV (DPP4) enzymatic activity in circulation have been proposed as biomarkers for colorectal cancer and other diseases. However, changes in sCD26 and DPP4 levels show complex degrees of correlation, and their physiological or pathophysiological role is unclear. The aim of this study was to analyse if anti-CD26 autoantibodies are related to sCD26 and DPP4 and to determine their relevance in a context of colorectal cancer screening for complementing the value of sCD26 and DPP4 as biomarkers. These biomarkers were measured in a large prospective cohort ( = 497, except the anti-CD26 antibodies, evaluated in 125 samples) that included a subgroup of individuals that were positive for the faecal immunological occult blood test (FIT) ( = 86) and underwent a colonoscopy ( = 47). We confirmed for the first time higher DPP4 activity in men compared to women (Student's test, = 0.002), though this difference between sexes was not seen for serum sCD26 protein. These biomarkers correlated ( = 0.246, = 0.003) only in women. Correlations were found between anti-CD26 isotypes but not with DPP4 activity or sCD26 concentration, except for a negative correlation only in men between anti-CD26 IgA isotype and sCD26 ( = -0.232, = 0.044), and an almost significant negative correlation between anti-CD26 IgG and sCD26 limited to FIT-positive men. Interestingly, patients with advanced adenomas displayed the most elevated mean levels of anti-CD26 IgA, IgM, and particularly IgG (Mann-Whitney test, = 0.030) in comparison with the other FIT positives without adenomas, and these levels did not correlate with sCD26 or its DPP4 activity. Our preliminary results suggest that the combination of these measures using sex as confounder could perhaps be used as biomarkers for colorectal disease. It also suggests that events affecting the gut influence the levels of anti-CD26 antibodies, which show little or no effect in antigen clearance. These findings should be confirmed in a larger cohort of individuals with colonoscopy. The physiological origin of the sex differences observed should be further addressed.
目前的筛查试验显示结直肠癌发病率和死亡率有所降低。然而，参与率往往较低，而基于血液的检测可以补充现有的筛查策略。循环中的 CD26 蛋白（sCD26）及其二肽基肽酶 IV（DPP4）酶活性已被提议作为结直肠癌和其他疾病的生物标志物。然而，sCD26 和 DPP4 水平的变化显示出复杂的相关性，其生理或病理生理学作用尚不清楚。本研究旨在分析抗 CD26 自身抗体是否与 sCD26 和 DPP4 相关，并确定其在结直肠癌筛查中补充 sCD26 和 DPP4 作为生物标志物的价值的相关性。在一个包含粪便免疫化学潜血试验（FIT）阳性亚组（=86）并接受结肠镜检查（=47）的大型前瞻性队列中（=497，除了抗 CD26 抗体，评估了 125 个样本）中测量了这些生物标志物。我们首次证实男性的 DPP4 活性高于女性（Student's 检验，=0.002），尽管男女之间的这种性别差异在血清 sCD26 蛋白中没有看到。这些生物标志物仅在女性中相关（=0.246，=0.003）。在抗 CD26 同种型之间发现了相关性，但与 DPP4 活性或 sCD26 浓度没有相关性，除了男性中抗 CD26 IgA 同种型与 sCD26 之间的负相关（= -0.232，=0.044），以及仅在 FIT 阳性男性中抗 CD26 IgG 与 sCD26 之间几乎显著的负相关。有趣的是，与其他无腺瘤的 FIT 阳性患者相比，进展性腺瘤患者的抗 CD26 IgA、IgM 特别是 IgG 水平显示出最高的平均水平（Mann-Whitney 检验，=0.030）。这些水平与 sCD26 或其 DPP4 活性没有相关性。我们的初步结果表明，使用性别作为混杂因素结合这些措施可能可以用作结直肠疾病的生物标志物。它还表明，影响肠道的事件会影响抗 CD26 抗体的水平，而这些抗体在抗原清除方面几乎没有影响。这些发现应在接受结肠镜检查的更大队列中得到证实。还应进一步解决观察到的性别差异的生理起源。
