Prognostic value of co-expression of STAT3, mTOR and EGFR in gastric cancer.

Signal transducer and activator of transcription 3 (STAT3), the mammalian target of rapamycin (mTOR) and epidermal growth factor receptor (EGFR), proteins that mediate intracellular signaling related to cell growth, proliferation and differentiation, have received considerable interest as possible targets for cancer treatment. We examined whether the expression of STAT3, mTOR and EGFR correlates with clinicopathological features and patient outcome in gastric cancer. Tumor samples were obtained from 126 patients with gastric adenocarcinomas who underwent a radical gastrectomy between 1999 and 2002. The expression of phosphorylated STAT3 (p-STAT3), p-mTOR and EGFR was analyzed by immunohistochemical staining. The relations of these to clinicopathological factors and outcomes were assessed. The expression of p-STAT3 p-mTOR and EGFR positively correlated with the following variables related to tumor progression: the depth of tumor invasion (T1 vs. T2-4; p<0.001, p=0.036 and p<0.001, respectively), lymph node involvement (p=0.008, p=0.027 and p=0.007) and tumor stage (I vs. II-IV; p<0.001, p=0.041 and p<0.001). The expression of p-STAT3 and EGFR was significantly related to distant metastasis and recurrence (p=0.001 and p=0.039), as well as significantly poorer disease-specific survival (DSS; p=0.0018 and p=0.026). The expression of p-STAT3 was a marginally non-significant prognostic factor for DSS (hazard ratio=2.0, 95% CI 0.91-4.5, p=0.082). Increasing expression of p-STAT3, p-mTOR and EGFR was associated with progressively worse DSS. Interactions among p-STAT3, p-mTOR and EGFR may play an important role in tumor progression and outcomes in patients with gastric cancer.