Suppression Decreases 5-Fluorouracil-induced Apoptosis and Is Associated With Poor Prognosis in Gastric Cancer.

BACKGROUND/AIM: The development of new biomarkers to predict cancer patient prognosis is expected to aid in treatment selection, contributing to improved outcomes. In this study, we extracted a candidate gene associated with patient prognosis from a public database and investigated the molecular and biological functions and clinical significance of the gene in gastric cancer.

MATERIALS AND METHODS

We analyzed The Cancer Genome Atlas database and identified the family with sequence similarity 32 member a (FAM32A) as a candidate gene. We investigated the clinicopathological significance of FAM32A mRNA and protein expression in 300 and 176 gastric cancer patients respectively. We evaluated the molecular and biological functions by suppressing FAM32A expression in gastric cancer cell lines using small interfering RNA.

RESULTS

In the polymerase chain reaction (PCR) cohort, low FAM32A expression group showed significantly shorter disease-specific survival (DSS) [hazard ratio (HR)=1.586; 95% confidence interval (95% CI)=1.056-2.382, p=0.026]. In the immunohistochemistry cohort, the FAM32A(-) group had significantly shorter overall survival (HR=1.703; 95% CI=1.050-2.764, p=0.031) and DSS (HR=2.123; 95% CI=1.185-3.804, p=0.011). Multivariate Cox hazard analysis revealed that FAM32A(-) was an independent adverse prognostic factor for DSS (p<0.001). AGS cell lines with FAM32A knockdown exhibited significant resistance to 5-fluorouracil (5-FU) and reduced apoptosis upon 5-FU administration. Gene set enrichment analysis indicated decreased gene expression related to the p53 signaling pathway in AGS cells with FAM32A knockdown that were treated with 5-FU.

CONCLUSION

FAM32A suppression decreases 5-FU-induced apoptosis. Low FAM32A expression is associated with a poor prognosis in gastric cancer, suggesting its potential as a biomarker.