An Fangmei, Zheng Chuwei, Zhang Guoqiang, Zhou Liangyun, Wu Yuqing, Hou Zheng, Zhou Zhiyi, Chen Ke, Zhan Qiang
Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, China.
Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China.
Front Oncol. 2021 Jun 17;11:643669. doi: 10.3389/fonc.2021.643669. eCollection 2021.
The diagnosis of precancerous lesions or early gastric cancer (EGC) is very important for patient survival. Molecular imaging is a visualized method that can easily and precisely diagnose tumors. However, there are currently few studies about molecular imaging diagnosis of EGC. Here, we studied the expression of carcinoembryonic antigen related cell adhesion molecule 6 (CEACAM6) in the progression of GC. Then, the regulatory roles of CEACAM6 in GC cells were investigated. Furthermore, both the fluorescent-labeled and near infrared molecular-labeled probes were synthesized, and the diagnostic value of anti-CEACAM6 probes in GC was evaluated using a GC mice model as well as using fresh dysplastic gastric mucosa obtained from endoscopic submucosal dissection (ESD) operations. Our study showed that CEACAM6 was over expressed in GC tissues compared to adjacent tissues, and the patients with higher CEACAM6 expression had lower survival time. Moreover, the CEACAM6 expression was higher in the dysplastic gastric mucosa than in the adjacent normal mucosa. CEACAM6 accelerated the growth, proliferation, and invasion of GC cells in the and studies. Moreover, up regulated CEACAM6 can induce the expression of proteins related to GC progression. Furthermore, the anti-CEACAM6 probes exhibited good affinity with GC cell lines. The probes can track tumors as well as metastases in the mice model , and can precisely identify the area of dysplastic gastric mucosa using specimens obtained from ESD operations by wide field fluorescent endoscopy. The surface micro features of the mucosa can also be observed using fluorescent micro endoscopy, and the degree of atypia can be distinguished by both the signal intensity and surface micro morphology. CEACAM6 is a key molecular marker in GC progression, and the anti-CEACAM6 probe-assisted fluorescent endoscopy may be a potential option for the diagnosis of precancerous lesions.
癌前病变或早期胃癌(EGC)的诊断对患者的生存至关重要。分子成像是一种可视化方法,能够轻松、精确地诊断肿瘤。然而,目前关于EGC分子成像诊断的研究较少。在此,我们研究了癌胚抗原相关细胞黏附分子6(CEACAM6)在胃癌进展过程中的表达。然后,研究了CEACAM6在胃癌细胞中的调控作用。此外,合成了荧光标记和近红外分子标记探针,并使用GC小鼠模型以及从内镜黏膜下剥离术(ESD)手术中获取的新鲜发育异常胃黏膜评估了抗CEACAM6探针在胃癌中的诊断价值。我们的研究表明,与相邻组织相比,CEACAM6在胃癌组织中过度表达,且CEACAM6表达较高的患者生存时间较短。此外,发育异常胃黏膜中的CEACAM6表达高于相邻正常黏膜。在体内和体外研究中,CEACAM6加速了胃癌细胞的生长、增殖和侵袭。此外,上调CEACAM6可诱导与胃癌进展相关的蛋白质表达。此外,抗CEACAM6探针与胃癌细胞系表现出良好的亲和力。该探针能够在小鼠模型中追踪肿瘤及转移灶,并可通过广角荧光内镜使用ESD手术获取的标本精确识别发育异常胃黏膜区域。使用荧光显微内镜还可观察黏膜的表面微观特征,并且可通过信号强度和表面微观形态区分异型程度。CEACAM6是胃癌进展中的关键分子标志物,抗CEACAM6探针辅助荧光内镜检查可能是诊断癌前病变的一种潜在选择。