De Chiara Loretta, Barcia-Castro Leticia, Gallardo-Gómez María, Páez de la Cadena María, Martínez-Zorzano Vicenta S, Rodríguez-Berrocal Francisco J, Bujanda Luis, Etxart Ane, Castells Antoni, Balaguer Francesc, Jover Rodrigo, Cubiella Joaquín, Cordero Oscar J
Department of Biochemistry, Genetics and Immunology, Universidade de Vigo, 36210 Vigo, Spain.
CINBIO, Universidade de Vigo, 36210 Vigo, Spain.
Cancers (Basel). 2022 Sep 20;14(19):4563. doi: 10.3390/cancers14194563.
Fecal hemoglobin immunodetection (FIT) in combination with endoscopy has been implemented to reduce mortality from colorectal cancer (CRC), although there are issues that can be improved in relation to participation rates. We studied whether the blood biomarker soluble-CD26 (sCD26), related at least in part to the immune system and inflammation, and/or its dipeptidyl peptidase enzyme activity (DPP4), could help reduce false positives. In a cohort of 1703 individuals who underwent colonoscopy and had a serum sample, sCD26 and DPP4 activity showed statistically significant differences regarding sex and age. According to the colonoscopy findings, sCD26 and DPP4 activity progressively decreased in advanced adenomas and CRC, with statistically significant differences, even between both groups; 918 of them had a FIT result ( = 596 positive cases) with approximately 70% of these ( = 412) false positives. With cut-offs of 440 ng/mL for sCD26, 42 mU/mL for DPP4, and 11 ng/mU for their ratio, the combined information of the three biomarkers (at least positive for one biomarker) identified almost all advanced adenomas and CRC cases in the FIT cohort with approximately half of the false positives compared to FIT. A sequential testing strategy with FIT and our blood biomarker test is proposed.
粪便血红蛋白免疫检测(FIT)与内镜检查相结合已被用于降低结直肠癌(CRC)的死亡率,尽管在参与率方面仍有可改进之处。我们研究了血液生物标志物可溶性CD26(sCD26)(至少部分与免疫系统和炎症相关)及其二肽基肽酶活性(DPP4)是否有助于减少假阳性。在一组1703名接受结肠镜检查并采集了血清样本的个体中,sCD26和DPP4活性在性别和年龄方面存在统计学显著差异。根据结肠镜检查结果,sCD26和DPP4活性在晚期腺瘤和CRC中逐渐降低,两组之间甚至存在统计学显著差异;其中918人有FIT结果(=596例阳性病例),其中约70%(=412)为假阳性。当sCD26的临界值为440 ng/mL、DPP4为42 mU/mL及其比值为11 ng/mU时,三种生物标志物的联合信息(至少一种生物标志物为阳性)在FIT队列中识别出了几乎所有晚期腺瘤和CRC病例,假阳性数量约为FIT的一半。我们提出了一种FIT与血液生物标志物检测的序贯检测策略。