TPK1 as a predictive marker for the anti-tumour effects of simvastatin in gastric cancer.

The potential anti-tumour role of statins has been reported in various cancer types, including gastric cancer (GC). However, there are no biomarkers to identify patients who may benefit most from this treatment. We tested the effects of statins on 8 GC cell lines. Genes differentially expressed in simvastatin-sensitive and -resistant cell lines were used to identify potential biomarkers of simvastatin sensitivity. Patient-derived cell lines were used to mimic in vivo conditions. In simvastatin-sensitive SNU-5 cells, the levels of the PARP and cleaved caspase-3 apoptosis markers increased upon exposure to simvastatin. The levels of the PARP and cleaved caspase-3 levels were unchanged by simvastatin exposure in simvastatin-resistant SNU-668 cells. The proportion of apoptotic cells was increased in SNU-5 cells but not in SNU-668 cells under the same drug exposure conditions. Comparison of differentially expressed genes (DEGs) in sensitive and resistant cell lines identified 31 genes potentially involved in the cellular response to simvastatin. We confirmed that RNA expression of the TPK1 DEG was significantly increased in simvastatin-sensitive cell lines. TPK1 knockdown in a simvastatin-sensitive GC SNU5 cell line, decreased the anti-tumour effects of simvastatin, while TPK1 overexpression enhanced the anti-tumour effect of simvastatin. Therefore, TPK1 expression can be used as a predictive marker of the anti-tumour effects of statin treatment in patients with cancer, especially in those with GC.