Oral mucin expression in the early diagnosis of esophagogastric cancer.

Abstract

e16099 Background: Challenges in early diagnosis of esophagogastric carcinoma (EGC) may partly explain its poor long-term survival and why only 37.5% of patients are eligible for potentially curative treatment with perioperative chemo(radio)therapy and surgical resection. A non-invasive risk stratification test that could identify patients with early EGC is urgently needed. Mucins MUC2 and MUC5AC are abundant in the oral cavity and the upper gastrointestinal (GI) tract. They may be implicated in EG tumorigenesis via pro-inflammatory pathways and interaction with the microbiome. This study examines whether salivary mucin expression could yield potential markers of early EGC. Methods: A multi-center observational cohort study was conducted at two specialist cancer centers in the UK following obtainment of ethical approval (Ref 23/PR/0816). Subjects with benign upper GI diseases including gastro-esophageal reflux, Barrett’s metaplasia or EGC were recruited. Whole saliva was collected immediately prior to upper GI endoscopy or surgery, and tissue biopsies during endoscopy or esophagogastrectomy. Clinical data including medications, oral health and smoking history were collected from all subjects. Expression of MUC2 and MUC5AC , and pro-inflammatory cytokines IL1β and IL6 were evaluated by RT-qPCR. The ability of salivary mucin expression to distinguish subjects with cancer from other recruited subjects was evaluated by receiver operating characteristic (ROC) analysis yielding area under the curve (AUC) values, and logistic regression in GraphPad Prism version 10.1.2. Statistical significance was confirmed when p< 0.05. Results: A total of n= 217 subjects were recruited: n= 47 with upper GI symptoms, n= 42 with Barrett’s metaplasia and n= 128 with EGC. Expression of salivary MUC2 mRNA was lower in Barrett’s metaplasia (p< 0.05) and treatment- naïve EG adenocarcinoma tissue (p< 0.05) compared to subjects with benign upper GI diseases. In comparison, MUC2 mRNA expression was higher in EG tumor tissue than in benign upper GI disease. Expression of IL1β and IL6 mRNA expression in tumor correlated positively with MUC2 mRNA in tumor (p< 0.05) suggesting an association between mucins and pro-inflammatory pathways in tumorigenesis. ROC curve analysis demonstrated that salivary MUC2 expression was able to distinguish subjects with esophageal and type 1-2 gastro- esophageal junction (GEJ) adenocarcinoma, and type 3 GEJ and gastric adenocarcinoma from benign upper GI diseases with an AUC of 0.912 and 0.968 (p< 0.0001). Univariate logistic regression showed that male gender (p= 0.00439) and smoking (p= 0.0208) were significantly associated with EGC. Conclusions: Salivary mucin expression can potentially distinguish subjects with EGC from those with benign upper GI diseases. This research forms the basis for further studies investigating the use of oral mucin expression in early diagnosis of EGC.