[Impact of S100P expression on clinical outcomes of gastric cancer patients with adjuvant chemotherapy of oxaliplatin and its mechanisms]

Abstract

Objective: To investigate the impact of the expression of S100P on the prognosis and tumor chemosensitivity in patients with resectable gastric cancer and its mechanisms.

Methods: The expression of S100P was analyzed in 121 resected primary gastric cancer tissues by using tissue array of immunohistochemistry excised from January 2003 to December 2007. The patients received adjuvant chemotherapy with oxaliplatin. The pEGFP-S100P plasmid was constructed and was transfected into BGC823 cell line to establish gastric cancer cell line with over-expression of human S100P, BGC823-S100P. The expression level of S100P was determined by real-time PCR and Western blot assay. The chemosensitivity of BGC823-S100P cell line to oxaliplatin was detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay.

Results: The S100P was positively expressed in 64 tumors (52.9%, 64/121). Although there was no significant relation between the expression of S100P and tumor T staging (P = 0.683), N staging (P = 0.472), M staging (P = 0.770) and differentiation (P = 0.553), Wilcoxon test showed that the 5-year cumulative survival rate of patients with positive S100P expression was significantly higher than that of patients with negative expression (20.3% vs. 3.5%, P = 0.034). Furthermore, overexpressed of S100P was found in the BGC823 cell line, BGC823-S100P. The mRNA and protein level of S100P in pEGFP transfected BGC823-S100P cell lines were significantly higher than those in control group (8.42 ± 1.38 vs. 0.83 ± 0.11 and 3.52 ± 0.48 vs. 0.97 ± 0.19, all P < 0.05). It indicated with MTT assay that the half-inhibitory concentration (IC(50)) to oxaliplatin decreased in BGC823-S100P cells, and was significantly lower than that in vector-only transfected cells [(142 ± 16) mg/L vs. (266 ± 11) mg/L, P = 0.032].

Conclusions: S100P may also be a potentially novel independent prognostic factor in gastric cancer patients following curative resection. And it could improve the cumulative survival of the patients through enhancing the chemosensitivity of tumor cell line to oxaliplatin.