Rapid and sensitive detection of early esophageal squamous cell carcinoma with fluorescence probe targeting dipeptidylpeptidase IV.
Rapid and sensitive detection of early esophageal squamous cell carcinoma with fluorescence probe targeting dipeptidylpeptidase IV.
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DOI：
10.1038/srep26399
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发表时间：
2016-06-01
影响因子：
4.6
通讯作者：
Seto Y
中科院分区：
文献类型：
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作者：
Onoyama H;Kamiya M;Kuriki Y;Komatsu T;Abe H;Tsuji Y;Yagi K;Yamagata Y;Aikou S;Nishida M;Mori K;Yamashita H;Fujishiro M;Nomura S;Shimizu N;Fukayama M;Koike K;Urano Y;Seto Y
早期发现食管鳞状细胞癌（ESCC）是一个重要的指标，但很难实现传统的内镜。传统的卢戈染色内镜和基于设备的图像增强内镜，如窄带成像（NBI），有各种实际的局限性。由于基于荧光的可视化被认为是一种有前途的方法，我们的目标是开发一种可激活的荧光探针来可视化ESCC。首先，基于各种氨肽酶活性在癌症中升高的事实，我们用一系列氨肽酶可激活的荧光探针筛选了来自患者的新鲜切除标本。结果表明，二肽基肽酶IV（DPP-IV）在食管鳞癌中被特异性激活，有望成为食管癌检测的一个合适的分子靶点。因此，我们设计、合成并表征了一系列DPP-IV可激活的荧光探针。将所选探针局部喷涂到内镜黏膜下剥离术（ESD）或手术标本上，肿瘤在5 min内可见，喷涂到活检标本上，敏感性、特异性和准确性分别达到96.9%、85.7%和90.5%。我们认为，DPP-IV靶向的可活化荧光探针实际上可作为临床应用的方便工具，以在内窥镜或外科手术过程中快速准确地诊断早期食管癌。
Early detection of esophageal squamous cell carcinoma (ESCC) is an important prognosticator, but is difficult to achieve by conventional endoscopy. Conventional lugol chromoendoscopy and equipment-based image-enhanced endoscopy, such as narrow-band imaging (NBI), have various practical limitations. Since fluorescence-based visualization is considered a promising approach, we aimed to develop an activatable fluorescence probe to visualize ESCCs. First, based on the fact that various aminopeptidase activities are elevated in cancer, we screened freshly resected specimens from patients with a series of aminopeptidase-activatable fluorescence probes. The results indicated that dipeptidylpeptidase IV (DPP-IV) is specifically activated in ESCCs, and would be a suitable molecular target for detection of esophageal cancer. Therefore, we designed, synthesized and characterized a series of DPP-IV-activatable fluorescence probes. When the selected probe was topically sprayed onto endoscopic submucosal dissection (ESD) or surgical specimens, tumors were visualized within 5 min, and when the probe was sprayed on biopsy samples, the sensitivity, specificity and accuracy reached 96.9%, 85.7% and 90.5%. We believe that DPP-IV-targeted activatable fluorescence probes are practically translatable as convenient tools for clinical application to enable rapid and accurate diagnosis of early esophageal cancer during endoscopic or surgical procedures.