Effects Of STAT3and CXCR3on Vasculogenic Mimicry In Gastric Adenocarcinoma Tissues And Clinical Pathological Significance

Objective:To observe the expression levels of signal transducer and activator of transcription3(STAT3), hypoxia-inducible factor-1α (HIF-1α) and CXC-chemokine receptor3(CXCR3) in gastric adenocarcinoma (GAC) tissues, investigate their effects on vasculogenic mimicry (VM) formation and analysis their relationships with clinicopathological parameters, then analysis the influence on patients’prognosis.Methods:The expression levels of STAT3, phosphor-STAT3.(p-STAT3), HIF-1α, CXCR3and interferon-inducible T cell alpha chemo attractant (I-TAC) were detected by immunohistochemically, and the VM formation was explored by CD31/PAS double staining in60GAC tissues and60pericarcinous tissues. The mRNA expressions of STAT3, HIF-1α and MMP-2were detected by Real-Time PCR in13fresh GAC tissues and13fresh adjacent gastric mucosa tissues. Analysis connection among the expressions of STAT3and CXCR3, the VM formation, the clinicpathological parameters and survival analysis by SPSS19.0software in60GAC tissues.Results:1. The expression of VM existed in GAC tissues (31.67%) rather than pericarcinous tissues (P<0.05).2. The expression levels of STAT3, p-STAT3, HIF-1α,CXCR3and I-TAC were higher in GAC tissues than those in pericarcinous tissues (P<0.05), the higher expression levels of STAT3and p-STAT3correlated with poor differentiation. The positive expression rates were81.67%,58.33%,63.33%,76.67%,71.67%in the order. The expressions of STAT3, p-STAT3and HIF-1α increased in lymphatic metastasis GAC tissue.3. The expression levels of STAT3, p-STAT3, HIF-1α, CXCR3and I-TAC were higher in VM positive GAC tissues than those in VM negative GAC tissues (P<0.05).4. The VM formation in GAC tissues showed positive correlation with STAT3, P-STAT3, HIF-1α, CXCR3and I-TAC (P<0.05); while HIF-la expression showed both positive correlations with STAT3and p-STAT3(P<0.05).5. The expression levels of STAT3, p-STAT3, HIF-1α, CXCR3, I-TAC and VM were associated with the overall survival (OS) of GAC patients (P<0.05). P-STAT3-VM-positive and HIF-1α-VM-positive expression heralded poorer prognosis than VM-positive only patients. However, only p-STAT3and VM expression were identified as the independent risk factors of GAC OS when analyzing with multivariate analysis.6. The expressions of STAT3、HIF-1α and MMP-2mRNA increased in fresh GAC tissues (P<0.05). There was positive connection between MMP-2mRNA and STAT3mRNA or HIF-1α mRNA (P<0.05).Conclusions:1. Higher expression levels of STAT3, HIF-1α and CXCR3played significantly indicating roles in VM formation of GAC tissues.2. The expressions of STAT3and p-STAT3increased especially in poorly differentiated GAC and herald poor prognosis.3. Higher expressions of STAT3, p-STAT3and HIF-1α indicated the better power of metastasis of GAC.4. VM and p-STAT3might be independent indicated factors of the OS of GAC patients.