胃癌中Hp感染和Stat3活化的临床病理意义及其对预后的影响

Clinicopathological and Prognostic Significance of H. pylori Infection and Constitutive Activation of Stat3 in Patients with Gastric Cancer

为检测胃癌组织中幽门螺杆菌(Helicobacter pylori,Hp)感染及细胞转导与转录激活因子3(signal transducer and activator of transcription 3,Stat3)的活化水平,探讨Hp感染和Stat3活化的相关性以及对胃癌的发生、发展及预后的影响。应用实时荧光定量PCR检测80例胃癌以及其中50例相应癌旁非癌组织中Hp的相对感染量,同时应用免疫组化EnVision法检测上述样本中活化的p-Stat3水平;并结合患者的临床病理及随访资料进行综合分析。结果显示,(1)胃癌组织中Hp相对感染量显著高于癌旁非癌组织;活化的p-Stat3水平也显著高于癌旁非癌组织(P<0.05)。(2)胃癌组织中Hp相对感染量及p-Stat3水平与患者年龄、性别及组织学分型无明显相关性(P>0.05);Hp相对感染量与胃癌的肿瘤浸润深度、淋巴结转移和TNM分期呈显著正相关(P<0.05),但与远处转移无明显相关性(P>0.05);活化的p-Stat3水平与胃癌的肿瘤浸润深度、远处转移和TNM分期存在明显正相关(P<0.05),但与淋巴结转移无明显相关性(P>0.05)。胃癌中Hp相对感染量与活化p-Stat3水平呈显著正相关(r=0.557,P<0.001)。(3)Kaplan-Meier生存分析显示,Hp相对感染量和p-Stat3的水平均与胃癌患者生存率呈显著负相关(P<0.05)。由此可知,胃癌中Hp感染与Stat3的活化有关,Hp感染可能通过触发Stat3的磷酸化,激活Stat3炎性信号通路,进而参与胃癌的发生发展及预后。Hp感染及Stat3的活化水平可能作为临床上评估胃癌进展及预后的潜在标志物。

To investigate the clinical significance and impact of Helicobacter pylori （H. pylori） infection and the levels of activated Stat3 （p-Stat3） on the pathogenesis, progression, and prognosis in patients with gastric cancer.Relative infection of H. pylori was examined in 80 cases of gastric cancer tissues （test group） and 50 cases of adjacent non-cancerous tissues （control group） using real-time PCR.Immunohistochemistry （IHC） was used to test the levels of p-Stat3 in above tissues.The correlations between H.pylori infection and activated p-Stat3 were analyzed versus clinicopathological parameters and patients′survival, respectively.The results showed that （1） The relative infection of H.pylori and the levels of active p-Stat3 in gastric cancer tissues were significantly higher than those in adjacent non-cancerous tissues, respectively （both P〈0.05）. （2） The relative infection of H.pylori and the levels of active p-Stat3 had no significant correlations with patients′age,gender and tumor differentiation,respectively （P〉0.05）;The relative infection of H.pylori showed positive correlations with tumor infiltration depth, lymph node metastasis and TNM stages, respectively （P〈0.05）,but not with the presence of distant metastasis （P〉0.05）;p-Stat3 levels showed significant differences among tumor infiltration depth, the presence of distant metastasis and TNM stages, respectively （P〈0.05）,but exhibited no association with lymph node metastasis （P〉0.05）.Furthermore,a positive correlation was observed between the H.pylori infection and the active p-Stat3 level in gastric cancer tissues. （3） Kaplan-Meier survival analyses indicated that both the H.pylori infection and the p-Stat3 level were negatively correlated with the total survival of gastric cancer patients,i.e.,the higher the magnitude of H.pylori infection or the higher the levels of p-Stat3,the lower the total survival,respectively （P〈0.05）.H.pylori infection is correlated with activated status of Stat3.H.pylori infection may trigger the phosphorylation of Stat3, activate the inflammatory Stat3 signaling pathway by which participates in the development,progression and prognosis of gastric cancer.Accordingly,H.pylori infection and activated status of Stat3 （p-Stat3） may potentially serve as clinical biomarkers in evaluating the progression and prognosis of gastric cancer.