Low expression of DLC1 is predictive of poor therapeutic efficiency of fluoropyrimidine and oxaliplatin as adjuvant chemotherapy in gastric cancer.

Abstract

The Rho-GTPase-activating protein, deleted in liver cancer-1 (DLC1), has been reported to be a tumor suppressor. However, the prognostic value of DLC1 in gastric cancer (GC) remains to be fully elucidated. Fluoropyrimidine-oxaliplatin (FP-LOHP) combination therapy has been widely used for the adjuvant chemotherapy of GC, however, no reliable marker has been identified to determine its efficiency. Thus, the present study performed a retrospective investigation involving 251 patients with stage IB-III GC, who received adjuvant chemotherapy following radical resection and 37 patients with stage IV GC, who underwent palliative resection. The expression of DLC1 was found to be reduced in the majority of GC samples (212/288 pairs of samples), compared with normal mucosa, in immunohistochemical analyses. Lower expression levels of DLC1 indicated a more advanced tumor-node-metastasis stage, increased lymph node metastasis, deeper tumor invasion, increased tumor size and a higher rate of distant metastasis. By contrast, relatively increased expression levels of DLC1 indicated a longer time to recurrence (TTR) [hazard ratio (HR), 2.232; P=0.004] and overall survival (OS) rate (HR, 2.910; P=0.001). Patients receiving FP-LOHP adjuvant chemotherapy were significantly less likely to suffer GC recurrence (P=0.001) and succumb to mortality (P=0.004), compared with those who received alternative chemotherapies. However, only the patients with DLC1-positive GC receiving FP-LOHP [DLC1 (+)/FP-LOHP (+)] exhibited a more favorable TTR and OS, compared with the patients with DLC1 (+)/FP-LOHP (−) (TTR, P=0.001; OS, P=0.020). No significant improvement in clinical outcome was observed in GC patients with low DLC1 receiving FP-LOHP treatment (TTR, P=0.270; OS, P=0.197). In conclusion, low expression of DLC1 correlated with GC progression and is predictive of higher rates of recurrence and mortality. Only patients with DLC1-positive GC may have an improved treatment outcome from the use of FP-LOHP as adjuvant chemotherapy.