Mucin 5AC is a sensitive surface marker for sessile serrated lesions: results from a systematic review and meta-analysis

Sessile serrated lesions (SSLs) are a class of colon polyps which are challenging to detect through current screening methods but are highly associated with colon cancer. We reasoned that a biomarker sensitive for SSLs would be clinically useful to improve detection. Recent endoscopic and histopathologic studies suggest that SSLs are associated with alterations in intestinal mucin expression but the frequency with which this occurs is not known. We performed a meta-analysis of available pathologic studies comparing mucin expression on SSLs to normal colonic mucosa, tubular adenomas (TAs), villous adenomas (VAs), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). We searched Medline, Pubmed, and Embase and found 440 publications in this topic, and 18 total studies met inclusion. We found that MUC5AC expression was more common in SSLs compared to normal colonic mucosa (OR=82.9, p<0.01), TAs (OR=11, p<0.01), and TSAs (OR=3.6, p=0.04). We found no difference in MUC5AC expression between SSLs versus HPs (OR=2.1, p=0.09) and no difference in MUC5AC expression between left colon and right colon HPs, with an OR=1.8, p=0.23. We found that MUC5AC expression was found commonly on VAs, SSLs, and TSAs while the frequency on colon cancers declined. MUC5AC is also upregulated in inflammatory bowel disease and in response to intestinal infections. MUC5AC expression highlights the potential of mucins as sensitive biomarkers, though not specific to SSLs. Further research into the clinical utilization of MUC5AC could enhance SSL detection. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement We gratefully acknowledge support from the Chairmans Circle Fund through the NYU Grossman School of Medicine Department of Medicine, support from the National Institutes of Health, National Institute of Allergy and Infectious Diseases [R21-AI176122] and National Center for Advancing Translational Sciences (NCATS), National Institutes of Health [KL2TR001446]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript