Biological Features of Gastric Cancer After Neoadjuvant Chemotherapy

Gastric cancer prognosis remains poor, and neoadjuvant chemotherapy (NAC) is not widely used in Japan. While docetaxel-based regimens have shown promise internationally, the biological basis of their efficacy is not fully understood.

We performed a transcriptomic analysis of tumor sections from 24 patients with gastric cancer who received docetaxel plus S-1 (DS) or docetaxel with cisplatin plus S-1 (DCS) as NAC between 2011 and 2015. Our goal was to identify key biological differences between pathologically responsive and non-responsive groups.

The non-responding group had a significantly worse prognosis (p=0.017) despite similar baseline patient characteristics. Their tumors were marked by enrichment of proliferation-related gene sets, and a low infiltration of CD8+ and CD4+ effector memory cells and dendritic cells. We found no difference in key immune pathways, such as interferon-γ and interferon-α response. A final key finding was the significantly lower expression of five genes, namely zinc finger protein 296 (ZNF296), RAS association domain family member 10 (RASSF10), exocyst complex component 3-like 1 (EXOC3L1), microtubule-associated tyrosine carboxypeptidase 2 (KIAA0895), and polypeptide N-acetylgalactosaminyltransferase 1 (GALNTL1), in the non-response group.

Our study suggests that the lack of NAC response to DS/DCS therapy is associated with increased tumor proliferation, a poor antitumor immune response, and the reduced expression of these five genes (ZNF296, RASSF10, EXOC3L1, KIAA0895 and GALNTL1). These genes represent promising candidates for further investigation as biomarkers for predicting treatment efficacy and as novel therapeutic targets.