Gastric cancer is the fourth most common cancer worldwide with approximately 930 000 newly diagnosed cases annually. 1 Compared with other cancers, morbidity rates are quite high (∼ 700 000/year), making gastric cancer the second most common cause of cancer death worldwide after lung cancer. 1

Following expansion of the primary tumor mass, cancer cells commonly invade through the muscularis mucosa and extravasate into blood vessels, thus promoting metastasis via lymphatic nodes and vessels. 2 Disseminating metastasis occurs in 80–90% of individuals with intestinal type gastric cancer who have a 5-year survival rate of 75% in those diagnosed in early stages, and less than 30% of those diagnosed in late stages. 3, 4 Compared with other cancers, a substantial proportion of gastric cancer patients who have undergone curative surgery develop recurrent disease. The use of histopathological features, such as depth of primary tumor and lymphonodal involvement as indicators of prognosis, has improved survival. However, in recent years new prognostic molecular markers have been sought, as it is anticipated that measurement of molecular markers would more accurately indicate long-term outcome. Molecular markers are classified as molecules (most commonly proteins) the expression of which is altered in cancer, and which are functionally related to the cancer phenotype. Thus, the presence or absence of molecular markers can be used as indicators in evaluating cancer patient prognosis. Although several molecular markers have been proposed as prognostic factors in gastric cancer patients, such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1-α (HIF-1-α) and p53, 5–7 none have been accepted into standard clinical practice; histopathological scoring therefore remains the standard protocol. Ideally, gastric molecular markers should accurately correlate with the well characterized tumor–node–metastasis (TNM) protocol for calculating prognosis of gastric cancer patients; that is, the degree of tumor depth (T1–4), presence or absence of metastatic sites (M0–1) and the degree of lymphatic invasion (N1–4) by the primary gastric tumor (Table 1). 8 The STAT proteins, of which there are seven members, are a family of transcription factors which regulate expression of genes involved in both normal and pathological cellular processes. Accumulating evidence has demonstrated that various STAT members, when chronically activated (by protein phosphorylation) or expressed (increased synthesis), can act as mediators of oncogenesis in a range of human malignancies. 9 This strong association with particularly epithelial cancers, and the extent of altered expression, suggests that certain family members might be useful prognostic markers or even therapeutic targets for cancer, because they are the focus of pathological signaling. Of the STAT family members, STAT3, is most commonly activated in human cancer. 9 Numerous in vitro studies have shown that STAT3 promotes proliferation and invasion of gastric cancer cells, 10, 11 and upregulates expression of potent angiogenic factors. 11 Additionally, it has been shown that STAT3 desensitizes cancer cells to anti-proliferative and apoptotic stimuli. 12, 13 As a transcription factor, STAT3 promotes cancer cell growth by upregulating the transcription of many well characterized genes including the matrix metalloproteinases (MMP), cyclins, VEGF and Src. 11–14 Furthermore, STAT3 has been shown to suppress expression of Fas, 15 thus reducing activity of apoptotic pathways (Table 1). In this issue of the Journal, Kim et al. extend …