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β-整联蛋白可作为结直肠癌的新型血清肿瘤标志物。

β -integrin serves as a novel serum tumor marker for colorectal carcinoma.

机构信息

Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

Department of Immunology, Stanford University, Stanford, CA.

出版信息

Int J Cancer. 2019 Aug 1;145(3):678-685. doi: 10.1002/ijc.32137. Epub 2019 Jan 29.

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide and the need for novel biomarkers and therapeutic strategies to improve diagnosis and surveillance is obvious. This study aims to identify β -integrin (ITGB6) as a novel serum tumor marker for diagnosis, prognosis, and surveillance of CRC. ITGB6 serum levels were validated in retro- and prospective CRC patient cohorts. ITGB6 serum levels were analyzed by ELISA. Using an initial cohort of 60 CRC patients, we found that ITGB6 is present in the serum of CRC, but not in non-CRC control patients. A cut-off of ≥2 ng/mL ITGB6 reveals 100% specificity for the presence of metastatic CRC. In an enlarged study cohort of 269 CRC patients, ITGB6 predicted the onset of metastatic disease and was associated with poor prognosis. Those data were confirmed in an independent, prospective cohort consisting of 40 CRC patients. To investigate whether ITGB6 can also be used for tumor surveillance, serum ITGB6-levels were assessed in 26 CRC patients, pre- and post-surgery, as well as during follow-up visits. After complete tumor resection, ITGB6 serum levels declined completely. During follow-up, a new rise in ITGB6 serum levels indicated tumor recurrence or the onset of new metastasis as confirmed by CT scan. ITGB6 was more accurate for prognosis of advanced CRC and for tumor surveillance as the established marker carcinoembryonic antigen (CEA). Our findings identify ITGB6 as a novel serum marker for diagnosis, prognosis, and surveillance of advanced CRC. This might essentially contribute to an optimized patient care.

摘要

结直肠癌(CRC)是全球癌症相关死亡的主要原因之一,显然需要新的生物标志物和治疗策略来改善诊断和监测。本研究旨在鉴定β-整合素(ITGB6)作为一种新的血清肿瘤标志物,用于 CRC 的诊断、预后和监测。验证了 ITGB6 血清水平在回顾性和前瞻性 CRC 患者队列中的作用。通过 ELISA 分析 ITGB6 血清水平。使用最初的 60 例 CRC 患者队列,我们发现 ITGB6 存在于 CRC 患者的血清中,但不存在于非 CRC 对照患者中。ITGB6 血清水平≥2ng/ml 的截断值对转移性 CRC 的存在具有 100%的特异性。在一个由 269 例 CRC 患者组成的扩大研究队列中,ITGB6 预测了转移性疾病的发生,并与不良预后相关。这些数据在由 40 例 CRC 患者组成的独立前瞻性队列中得到了证实。为了研究 ITGB6 是否也可用于肿瘤监测,我们评估了 26 例 CRC 患者术前、术后以及随访期间的血清 ITGB6 水平。完全肿瘤切除后,ITGB6 血清水平完全下降。在随访期间,ITGB6 血清水平的新升高表明肿瘤复发或新转移的发生,这通过 CT 扫描得到了证实。与已确立的标志物癌胚抗原(CEA)相比,ITGB6 对晚期 CRC 的预后和肿瘤监测更准确。我们的研究结果确定 ITGB6 为一种新的用于诊断、预后和监测晚期 CRC 的血清标志物。这可能会极大地促进患者护理的优化。

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