Endoscopic surgery is increasingly utilized for the treatment of early gastric cancer (EGC) worldwide, whereas lymph node metastasis (LNM) remains a critical risk factor for the relapse of EGC after endoscopic surgery. Therefore, identifying potential predictive factors and understanding the molecular mechanisms are urgently needed for improving the outcome of EGC patients with LNM. UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme in the process of biosynthesis of CMP-Neu5Ac from UDP-N-acetylglucosamine (UDP-GlcNAc), which acts as a substrate for several reactions in glycan metabolism. In this study, we found that GNE was down-regulated in EGC patients with LNM. GNE expression as well as localization, tumor size, intravascular tumor thrombi and Lauren’s classification were further identified as independent predictive factors for LNM. Combining GNE expression with traditional risk factors, including tumor size and differentiation degrees, could generate a better model for predicting LNM in EGC patients. Overall, our study implies that low GNE expression is a potential predictor of LNM in EGC.

Cuproptosis is a newly defined programmed cell death pattern and is believed to play an important role in tumorigenesis and progression. In addition, many studies have shown that glycosylation modification is of vital importance in tumor progression. However, it remains unclear whether glycosyltransferases, the most critical enzymes involved in glycosylation modification, are associated with cuproptosis. In this study, we used bioinformatic methods to construct a signature of cuproptosis-related glycosyltransferases to predict the prognosis of colon adenocarcinoma patients. We found that cuproptosis was highly correlated with four glycosyltransferases in COAD, and our model predicted the prognosis of COAD patients. Further analysis of related functions revealed the possibility that cuproptosis-related glycosyltransferase Exostosin-like 2 (EXTL2) participated in tumor immunity.