Identification and validation of serum MUC17 as a non-invasive early warning biomarker for screening of gastric intraepithelial neoplasia

Background: The early diagnosis and treatment of Gastric Intraepithelial Neoplasia (GIN) are pivotal for improving the survival rates of patients with gastric cancer (GC). Regrettably, reliable noninvasive biomarkers for GIN screening are currently lacking.

Methods: mRNA data from the GEO database, pan-cancer data from the TCGA database, and a gene list of exocrine proteins were subjected to integrated analysis to identify a noninvasive biomarker for GIN. The scRNA-seq data analysis, IHC and Elisa were employed to validate the expression of the biomarker in the serum and tissues of clinical patients across different pathological stages.

Results: MUC17 has been identified as a non-invasive diagnostic marker for GIN. It is upregulated in GIN prior to the onset of gastric carcinogenesis and downregulated in other tumors, with high GC specificity. The area under the curve values of serum MUC17 for differentiating chronic gastritis (CG) from low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and early gastric cancer (EGC) were 0.8788, 0.8544, and 0.9513, respectively. Additionally, low plasma MUC17 levels were found to be significantly lower in gastric ulcer (GU), gastric neuroendocrine tumor (GNET), and gastrointestinal stromal tumor (GIST) compared to GIN. The AUC for differentiating between GIN and GU, GNET, or GIST was 0.7803, 0.9244 and 0.9796, respectively.

Conclusions: These findings suggest that plasma MUC17 levels hold substantial promise as a screening biomarker for individuals with GIN and EGC, effectively identifying high-risk groups that necessitate further gastroscopy.