CD26-Related Serum Biomarkers: sCD26 Protein, DPP4 Activity, and Anti-CD26 Isotype Levels in a Colorectal Cancer-Screening Context
CD26-Related Serum Biomarkers: sCD26 Protein, DPP4 Activity, and Anti-CD26 Isotype Levels in a Colorectal Cancer-Screening Context
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DOI：
10.1155/2020/4347936
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发表时间：
2020-01-21
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影响因子：
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通讯作者：
Cordero, Oscar J.
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作者：
De Chiara, Loretta;Paez de la Cadena, Maria;Cordero, Oscar J.
目前的筛查试验显示结直肠癌的发病率和死亡率有所下降。然而，参与率往往较低，基于血液的检测可以补充现有的筛查策略。 CD26 蛋白 (sCD26) 及其循环中的二肽基肽酶 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程度的相关性，并且它们的生理或病理生理作用尚不清楚。本研究的目的是分析抗 CD26 自身抗体是否与 sCD26 和 DPP4 相关，并确定它们在结直肠癌筛查背景下的相关性，以补充 sCD26 和 DPP4 作为生物标志物的价值。这些生物标志物在一个大型前瞻性队列中进行了测量（n=497，抗 CD26 抗体除外，在 125 个样本中进行了评估），其中包括粪便免疫潜血试验 (FIT) 呈阳性的个体亚组 (n=86) 并接受了结肠镜检查 (n=47)。我们首次证实男性的 DPP4 活性高于女性（学生 t 检验，p=0.002），尽管血清 sCD26 蛋白没有发现性别之间的差异。这些生物标志物仅在女性中相关（R=0.246，p=0.003）。发现抗CD26同种型之间存在相关性，但与DPP4活性或sCD26浓度无关，除了仅在男性中抗CD26 IgA同种型和sCD26之间存在负相关（R=-0.232，p=0.044），并且抗CD26 IgG和sCD26之间几乎显着的负相关仅限于FIT阳性男性。有趣的是，与其他无腺瘤的 FIT 阳性患者相比，晚期腺瘤患者的抗 CD26 IgA、IgM、尤其是 IgG 的平均水平最高（Mann-Whitney U 检验，p=0.030），并且这些水平与 sCD26 或其 DPP4 活性无关。我们的初步结果表明，使用性别作为混杂因素的这些措施的组合也许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，而抗 CD26 抗体对抗原清除影响很小或没有影响。这些发现应该在更大的结肠镜检查人群中得到证实。应进一步解决所观察到的性别差异的生理起源。
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 (n=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) (n=86) and underwent a colonoscopy (n=47). We confirmed for the first time higher DPP4 activity in men compared to women (Student's t test, p=0.002), though this difference between sexes was not seen for serum sCD26 protein. These biomarkers correlated (R=0.246, p=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 (R=-0.232, p=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 U test, p=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.