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Updated: May 24, 2025
Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
Published on: May 10, 2024
Expression of the Niemann-Pick C1-like 1 Protein in Gastric Cancer
Takeharu Imai1,2, Manabu Futamura3, Ryutaro Mori3
1Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, Gifu, Japan; qqzv23py9@yahoo.co.jp.
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.
Insights
This study investigated genes linked to 5-Fluorouracil (5-FU) resistance in gastric cancer (GC). While NPC1L1 did not directly cause resistance, its elevated expression in GC tissues correlates with poorer patient prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- 5-Fluorouracil (5-FU) is a key treatment for gastric cancer (GC).
- Drug resistance to 5-FU presents a significant clinical challenge in GC management.
- Identifying genes associated with 5-FU resistance is crucial for improving treatment strategies.
Purpose of the Study:
- To identify genes contributing to 5-FU resistance in gastric cancer.
- To investigate the role and expression patterns of candidate genes in GC tissues.
- To assess the prognostic significance of identified genes in GC patients.
Main Methods:
- Gene expression analysis was performed on 5-FU-resistant (MKN-45/F2R) and parental (MKN-45) gastric cancer cells.
- Expression levels were compared before and after 5-FU treatment.
- NPC1L1 expression was examined in GC cell lines and patient tumor tissues using mRNA analysis and immunohistochemistry.
Main Results:
- NPC1L1 did not demonstrate a direct role in 5-FU resistance in the tested cell lines.
- NPC1L1 mRNA was detected in normal gastric tissues and various organs, with elevated levels in several GC samples.
- Immunostaining revealed NPC1L1 expression in 41.0% of GC patient tumors, correlating with poorer prognoses.
Conclusions:
- NPC1L1 is expressed in normal and GC tissues.
- Elevated NPC1L1 expression at invasive sites in GC is associated with unfavorable patient outcomes.
- NPC1L1 may serve as a potential prognostic biomarker in gastric cancer.
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