STAT3 activation in tumor cell-free lymph nodes predicts a poor prognosis for gastric cancer

STAT3 is constitutively activated in many human cancers including gastric cancer and plays crucial roles in modulating cancer cell proliferation, survival, metastasis as well as the microenvironment of pre-metastatic niches. Accumulating evidence has implicated STAT3 as a promising target for cancer therapy and it has been well established that tumor cell metastasized to lymph node is associated with poor prognosis. However, little is known about the relation between STAT3 activation in tumor cell-free lymph nodes and patient clinical outcomes. The objective of the current study was to investigate the role of STAT3 activity in tumor cell-free lymph nodes in tumor progression and prognosis for gastric cancer patients. Immunohistochemical analyses for p-STAT3, Ki-67, CD68 and Bcl-xL were performed in tumor cell-free lymph nodes from 60 gastric cancer patients. Survival analysis was conducted by using the Kaplan-Meier method. Immunohistochemical analyses showed that hyperactivity of STAT3 in tumor cell-free lymph nodes was significantly associated with tumor recurrence, and STAT3 activation pattern coincides with expression Ki-67, CD68, Bcl-xL. Survival analysis revealed that persistent STAT3 activation in uninvolved lymph nodes was positively associated with poor overall survival (P<0.05). These findings suggest that STAT3 activation in tumor-free lymph nodes is involved in the pathogenesis and metastasis of gastric cancer and that elevated STAT3 activity in lymph nodes prior to tumor cell arrival may indicate a poorer prognosis. These clinical studies support our findings in mouse tumor models showing that STAT3 activation is crucial for pre-metastatic niche formation and metastasis.