Abstract
Vasculogenic mimicry (VM) formation is important for invasion and metastasis of tumor cells in gastric adenocarcinoma (GAC). The present study aimed to investigate the association between signal transducer and activator of transcription-3 (STAT3), phosphor-STAT3 (p-STAT3), hypoxia-inducible factor-1α (HIF-1α) and VM formation in GAC, and discuss their clinical significance and correlation with the prognosis of patients with GAC. The expression levels of STAT3, p-STAT3, HIF-1α and VM were assessed in 60 cases of patients with GAC and 20 cases of patients with gastritis on tissue microarrays by immunohistochemical methods. The expression levels of STAT3, p-STAT3, HIF-1α and VM were higher in patients with GAC (particularly in poorly differentiated GAC) than in those with gastritis (P<0.05). The expression levels of STAT3, p-STAT3 and HIF-1α were higher in VM tissues compared with non-VM tissues (P<0.05). Positive correlations existed between STAT3, p-STAT3, HIF-1α and VM expression (P<0.05). The expression levels of STAT3, p-STAT3 and HIF-1α, VM, status of lymph node metastasis and tumor differentiation degree were associated with the overall survival time of patients with GAC (P<0.05). However, only p-STAT3 and VM expression were identified as the independent risk factors of GAC OS when analyzed with multivariate analysis. p-STAT3 and VM play a significant role in indicating the prognosis of patients with GAC. STAT3 activation may play a positive role in VM formation of GAC by the STAT3-p-STAT3-HIF-1α-VM effect axis.
Highlights
A blood supply is essential for the growth and hematogenous metastasis of tumors
Positive expression levels of signal transducer and activator of transcription‐3 (STAT3), p‐STAT3 and hypoxia‐inducible factor‐1α (HIF‐1α) were significantly increased in the gastric adenocarcinoma (GAC) specimens compared with the gastritis specimens, respectively (81.7 vs. 15.0, 58.3 vs. 5.0 and 63.3 vs. 10.0%; P
STAT3‐ and p‐STAT3‐positive expression and vasculogenic mimicry (VM) formation were increased in poorly differentiated GAC tissues compared with those in well‐differentiated GAC tissues, separately
Summary
A blood supply is essential for the growth and hematogenous metastasis of tumors. Maniotis et al [1] previously reported an angiogenesis‐independent pathway known as vasculogenic mimicry (VM) This pathway is a novel phenomenon in which highly aggressive human melanoma cells imitate endothelial cells and form vascular channel‐like structures to convey blood plasma and red blood cells without the involvement of endothelial cells. Periodic acid‐Schiff (PAS)‐positive patterns identify VM channels. VM was identified in lung cancer, hepatocellular carcinoma, gallbladder carcinoma, gastric adenocarcinoma (GAC) and other types of cancer [2,3,4,5]. VM may play an extremely significant role in the biological behavior of multiple tumors [2,3,4,5,6]. Establishing the detailed mechanism of VM formation is required
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