Upregulation of NPC1 and its association with poor prognosis in gastric cancer.

ABSTRACT

BACKGROUND: The Niemann-Pick disease type C1 (NPC1) protein plays a pivotal role in lipid transport, particularly free cholesterol, within lysosomal/late endosomal membranes. Previous studies have highlighted NPC1 as a promising target for cholesterol trafficking and cancer therapy. Nevertheless, the expression of NPC1 in gastric cancer (GC) and its clinical implications remain unexplored. This study aims to investigate NPC1 expression in GC and its correlation with patient prognosis. METHODS: NPC1 expression levels in GC and normal tissues were assessed using the GEPIA database, and survival analysis was conducted via Kaplan‒Meier Plotter. Evaluation of potential biological effects of NPC1 in GC by protein-protein interaction network and GO, KEGG bioenrichment analysis. Immunohistochemistry was performed on surgical samples collected from 306 GC patients. Correlations between NPC1 expression, clinical characteristics, and patient prognosis were analyzed. RESULTS: NPC1 mRNA expression was elevated in GC tissues compared to normal tissues (P < 0.05) and significantly associated with poorer prognosis. In our cohort of 306 patients, NPC1 exhibited significant upregulation in GC versus adjacent normal tissues (P = 0.031). High NPC1 expression correlated with adverse clinical characteristics, including lymph node metastasis, distant metastasis, and advanced TNM stage (all P < 0.05). Patients with high NPC1 expression experienced notably shorter overall survival (P < 0.001), particularly in stages III and IV (P = 0.003). Multivariate Cox regression analysis identified high NPC1 expression as an independent prognostic factor for GC patients (HR 1.57, 95% CI 1.14-2.18, P = 0.006). Lastly, an optimized nomogram incorporating NPC1, tumor size, and TNM stage was constructed. CONCLUSIONS: NPC1 expression is upregulated in GC and serves as a pivotal prognostic factor for adverse outcomes in GC patients.