Expression of the Niemann-Pick C1-like 1 Protein in Gastric Cancer.

[BACKGROUND/AIM] 5-Fluorouracil (5-FU) plays a major role in the treatment of gastric cancer (GC), and overcoming resistance to this drug remains a critical challenge. This study aimed to identify genes associated with resistance to 5-FU in GC.

[MATERIALS AND METHODS] Gene expression levels were analyzed in 5-FU-resistant MKN-45/F2R cells compared to the parental MKN-45 strain before and after 5-FU treatment (24 and 72 h). Among the consistently over-expressed genes, those with high expression were further investigated for their roles in resistance and expression patterns in GC tissues.

[RESULTS] NPC1L1, a protein hypothesized to influence 5-FU resistance, did not exhibit resistance-related effects in tested cells. Its expression was subsequently studied in gastric cells. NPC1L1 was detected in the stomach, jejunum, duodenum, and liver, with increased mRNA levels in several GC samples. Immunostaining of samples from 95 GC patients revealed that 39 (41.0%) exhibited ≥10% higher NPC1L1 expression. Patients with NPC1L1-positive tumors had poorer prognoses than those with negative tumors.

[CONCLUSION] NPC1L1 is expressed in both normal gastric tissues and GC tissues, with elevated levels at invasive sites associated with poor prognosis.