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目的:研究低氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)和轴突诱导因子4D(Semaphorin 4D,Sema4D)在胰腺癌组织中的表达,探讨两者之间的相关性及其临床意义。方法:采用免疫组织化学(immunohistochemistry,SP)法检测天津医科大学附属肿瘤医院和邯郸市中心医院82例胰腺癌组织和相应癌旁组织中HIF-1α和Sema4D的表达,采用Chi-square检验分析HIF-1α和Sema4D在不同组织中的表达差异,采用Chi-square检验分析HIF-1α和Sema4D与患者的性别、年龄、分化程度、肿瘤大小、胰腺癌分期、淋巴结转移、神经受侵、脉管内瘤栓等的相关性。HIF-1α和Sema4D在胰腺癌组织中的表达的相关性采用Mc Nemar检验分析其相关性。HIF-1α和Sema4D对胰腺癌患者生存率的影响分析采用Kaplan-meier法,生存曲线的比较采用Log-rank检验。Cox回归模型多因素分析方法,分析HIF-1α和Sema4D是否胰腺癌独立预后因素。结果:HIF-1α和Sema4D的阳性表达主要在细胞质内,呈棕黄色颗粒。HIF-1α和Sema4D在胰腺癌组织中的阳性表达率分别为52.4%(43/82)和51.2%(42/82),显著高于两者在癌旁组织的表达,差异有统计学意义(P<0.05)。HIF-1α的异常表达与胰腺癌分期(χ~2=11.398,P=0.000)、淋巴结转移(χ~2=20.341,P=0.000)、神经受侵(χ~2=23.478,P=0.000)、脉管内瘤栓(χ~2=8.281,P=0.000)相关,Sema4D的异常表达与胰腺癌分期(χ~2=7.212,P=0.007)、淋巴结转移(χ~2=60129,P=0.013)、神经受侵(χ~2=25.794,P=0.000)、脉管内瘤栓(χ~2=6.678,P=0.010)相关。HIF-1α和Sema4D的表达之间存在正相关性(κ=0.438,P=0.000)。单因素生存分析HIF-1α(χ~2=12.098,P=0.001)、Sema4D(χ~2=9.644,P=0.002)是影响胰腺癌的预后因素,Cox分析显示2者均不是影响胰腺癌的独立预后因素。结论:胰腺癌组织中存在HIF-1α和Sema4D表达的上调,两者具有明显相关性,与胰腺癌淋巴结转移、神经受侵、脉管内瘤栓有关,HIF-1α、Sema4D的表达可能提示胰腺癌患者分期较晚和预后不良。
OBJECTIVE: To investigate the expression of hypoxia inducible factor-1α (HIF-1α) and adenosine-inducing factor 4D (Sema4) in pancreatic cancer and to explore their correlations. Clinical significance. METHODS: Immunohistochemistry (SP) was used to detect the expression of HIF-1α and Sema4D in 82 cases of pancreatic cancer tissues and corresponding paraneoplastic tissues from the Affiliated Tumor Hospital of Tianjin Medical University and Central Hospital of Handan. Chi-square test was used to analyze HIF. Differences in expression of -1α and Sema4D in different tissues, Chi-square test was used to analyze the gender, age, differentiation, tumor size, stage of pancreatic cancer, lymph node metastasis, nerve invasion, and intravascular tumors of HIF-1α and Sema4D. Corking and other related. The correlation between the expression of HIF-1α and Sema4D in pancreatic cancer tissues was analyzed by Mc Nemar test. The influence of HIF-1α and Sema4D on the survival rate of patients with pancreatic cancer was analyzed by Kaplan-meier method. The survival curve was compared by Log-rank test. Cox regression model was used for multivariate analysis to analyze whether HIF-1α and Sema4D were independent prognostic factors of pancreatic cancer. RESULTS: The positive expression of HIF-1α and Sema4D was mainly in the cytoplasm with brownish yellow particles. The positive expression rates of HIF-1α and Sema4D in pancreatic cancer tissues were 52.4% (43/82) and 51.2% (42/82), respectively, which were significantly higher than those in the adjacent tissues. The difference was statistically significant ( P<0.05). The abnormal expression of HIF-1α and pancreatic cancer staging (χ~2=11.398, P=0.000), lymph node metastasis (χ~2=20.341, P=0.000), nerve invasion (χ~2=23.478, P=0.000) Intravascular tumor thrombi (χ~2=8.281, P=0.000) were associated with abnormal expression of Sema4D and pancreatic cancer staging (χ~2=7.212, P=0.007), lymph node metastasis (χ~2=60129, P=0.013). ), nerve invasion (χ~2=25.794, P=0.000), intravascular tumor thrombosis (χ~2=6.678, P=0.010). There was a positive correlation between the expression of HIF-1α and Sema4D (κ=0.438, P=0.000). Univariate survival analysis showed that HIF-1α (χ~2=12.098, P=0.001) and Sema4D (χ~2=9.644, P=0.002) were prognostic factors affecting pancreatic cancer. Cox analysis showed that neither of them affected pancreatic cancer. Independent prognostic factors. Conclusion: There is an up-regulation of HIF-1α and Sema4D expression in pancreatic cancer tissues. The two are significantly related to lymph node metastasis, nerve invasion, and intravascular tumor thrombus in pancreatic cancer. The expression of HIF-1α and Sema4D may indicate pancreatic cancer. Patients have a later stage and poor prognosis.