Prognostic and clinical significance of STAT3 and MMP9 in patients with gastric cancer: a meta-analysis of a Chinese cohort.

As signal transducer and activator of transcription 3 (STAT3)-mediated signaling cascade directly contributes to tumor metastasis, numerous agents targeting STAT3 are in clinical development. However, reported data on the prognostic impact of STAT3 expression vary considerably. We aim to quantitatively summarize available evidences for evaluating the association between STAT3 and STAT3-regulated target gene, matrix metalloproteinase 9 (MMP9), and the prognosis of Chinese patients with gastric cancer. Searches were applied to PubMed and the Chinese National Knowledge Infrastructure database without any language restriction. A total of 5,757 patients were included in the final analyses. All results favored an association between high STAT3 expression and poor 5-year overall survival (risk ratio = 1.845, 95% confidence interval [CI] = 1.027-3.315). The reduced survival was heavily influenced by advanced tumor invasion (OR = 2.885, 95% CI = 2.034-4.094), lymph node metastasis (OR = 5.349, 95% CI = 3.807-7.516), distant metastasis (OR = 5.873, 95% CI = 2.641-13.062), dedifferentiation (OR = 2.516, 95% CI = 1.814-3.491), tumor size (OR = 1.918, 95% CI = 1.246-2.954), and higher TNM stage (OR = 4.171, 95% CI = 2.840-6.126). Similar results were observed in the meta-analyses of MMP9, with the magnitude of effect OR > 2. Our findings indicate that STAT3 and MMP9, as measured by IHC, are associated with worse survival and potentially mark invasion and metastasis in gastric cancer, especially in Chinese patients. More significantly, these two biomarkers may be converted from candidates to the routine clinical evaluation to help predict the outcome of gastric carcinoma patients.