Abstract
BackgroundExploratory biomarker analysis was conducted to identify factors related to the outcomes of patients with stage II/III gastric cancer using data from the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer, which was a randomized controlled study comparing the administration of an orally active combination of tegafur, gimeracil, and oteracil with surgery alone.MethodsFormalin-fixed paraffin-embedded surgical specimens from 829 patients were retrospectively examined, and 63 genes were analyzed by quantitative real-time RT-PCR after TaqMan assay-based pre-amplification. Gene expression was normalized to the geometric mean of GAPDH, ACTB, and RPLP0 as reference genes, and categorized into low and high values based on the median. The impact of gene expression on survival was analyzed using 5-year survival data. The Benjamini and Hochberg procedure was used to control the false discovery rate.ResultsIGF1R and AREG were most strongly correlated with overall survival, which was significantly worse in high IGF1R patients than low IGF1R patients, but better in high AREG patients than low AREG patients. The hazard ratio for death in the analysis of overall survival (S-1 vs. surgery alone) was reduced in the high IGF1R group compared with the low IGF1R group and in the low AREG group compared with the high AREG group. There were no significant interaction effects.ConclusionIGF1R gene expression was associated with poor outcomes after curative resection of stage II/III gastric cancer, whereas AREG gene expression was associated with good outcomes. No significant interaction effect on survival was evident between S-1 treatment and gene expression.
Highlights
Despite a decreasing trend in Japan, gastric cancer remains the second most common cause of cancer-related death worldwide
This study retrospectively evaluated the influence of the expression levels of 63 preselected genes on the outcomes of patients enrolled in the ACTS-GC
We found an association between high IGF1R or low AREG expression and poor prognosis
Summary
Despite a decreasing trend in Japan, gastric cancer remains the second most common cause of cancer-related death worldwide. The 5-year overall survival (OS) rate in patients with stage IIIB disease was 50.2 % in the S-1 group in a subset analysis, suggesting room for improvement. This finding highlighted the need to identify the factors influencing relapse to develop more effective treatments for high-risk gastric cancer patients. Exploratory biomarker analysis was conducted to identify factors related to the outcomes of patients with stage II/III gastric cancer using data from the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer, which was a randomized controlled study comparing the administration of an orally active combination of tegafur, gimeracil, and oteracil with surgery alone. Conclusion IGF1R gene expression was associated with poor outcomes after curative resection of stage II/III gastric
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