Assessing the impact of GXYLT2 knockdown on the expression levels of genes associated with malignant characteristics, including proliferation, invasion, and stemness, in HGC-27 gastric cancer cells.

ABSTRACT: Gastric cancer ranks among the top ten most prevalent tumors worldwide, characterized by substantial heterogeneity and diverse morphological manifestations. Although postoperative histopathological examination serves as the cornerstone for determining Lauren classification, there exists a notable time lag in acquiring Lauren grade through this method. Furthermore, the invasiveness of detection techniques and limited tissue specimens markedly compromise the diagnostic precision of Lauren classification. Moreover, distinct molecular expression profiles exist between intestinal and diffuse types, yet the lack of molecular markers hampers the identification of these subtypes and their underlying mechanisms. Hence, our objective is to unearth biomarkers capable of distinguishing between intestinal and diffuse types and elucidate their mechanistic underpinnings, thereby refining the accuracy and applicability of Lauren classification. This pursuit holds promise for informing prognosis and optimizing treatment strategies for gastric cancer patients. Glycosylation emerges as a pivotal player in gastric cancer pathogenesis. Leveraging bioinformatics analyses on publicly available gastric cancer databases, we identified, at the transcriptomic level, elevated expression of the glycosylation-associated gene GXYLT2 in the diffuse subtype compared to the intestinal subtype. Subsequently, we corroborated these findings at both cellular and clinical tissue levels. Notably, GXYLT2 knockdown attenuated the proliferative, invasive, and sphere-forming capacities of gastric cancer cells in vitro. RNA-seq analysis and cellular validation unveiled that GXYLT2 depletion operates through inhibition of the Wnt/β-catenin signaling pathway. Encouragingly, in vivo validation demonstrated that GXYLT2 knockdown impedes gastric cancer growth. In conclusion, our study positions GXYLT2 as a potential biomarker capable of discerning between intestinal and diffuse subtypes, with prognostic implications in gastric cancer. Furthermore, we elucidate its role in gastric cancer progression via modulation of the Wnt/β-catenin signaling pathway.

ORGANISM(S): Homo sapiens

PROVIDER: GSE267825 | GEO | 2024/10/19

REPOSITORIES: GEO