Abstract
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 in vivo using a GC mice model as well as in vitro 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 in vitro and in vivo 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 in vivo, 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.
Highlights
Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide [1]
Data from TCGA showed that carcinoembryonic antigen related cell adhesion molecule 6 (CEACAM6) mRNA is up regulated in cancer tissues compared to their levels in normal tissues in stomach adenocarcinoma (Figure 1A)
In order to investigate the expression and possible role of CEACAM6 in gastric mucosa carcinogenesis, the mRNA sequencing was performed on gastric mucosa specimens with Chronic Superficial Gastritis (CSG), Chronic Atrophic Gastritis (CAG)+Intestinal Metaplasia (IM), Dys, and Cancer, and the genes of carcinoembryonic antigen (CEA) family member were verified by RT-qPCR method
Summary
Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide [1]. GC (EGC) has a 5-year survival rate that is more than 90%; by contrast, it is less than 20% in patients with advanced GC (AGC) [4, 5]. It is important to diagnose GC at the very early stages. Endoscopy-assisted pathology is currently the key diagnostic method for EGC; the preneoplastic lesion features are sometimes atypical under endoscopy in some cases. The new type of endoscopies such as high-resolution endoscopy, chromoendoscopy, magnification endoscopy, fluorescence endoscopy, narrow-band imaging, optical coherence tomography, point spectroscopy, and confocal laser endomicroscopy have been developed very well, the positive detection rate often depends on the experiences of operators. It may sometimes be difficult to find the lesions. Finding an easy and precise method to detect lesions during EGC is of urgent importance
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