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[摘要]
目的:研究胃腺癌中HIF-1α、EGFR蛋白的表达与胃癌病理特征及预后的关系。方法:收集南阳医学高等专科学校第一附属医院普外科于2008年7月至2010年7月手术切除的胃癌标本116例(其中管状腺癌和乳头状腺癌88例,黏液腺癌和印戒细胞癌28例),同时另取其中20例癌旁组织标本作为对照。采用免疫组织化学法检测胃腺癌组织和癌旁组织中HIF-1α、EGFR蛋白的表达,并分析其与临床病理因素及生存期的关系。结果: HIF-1α蛋白(63.8%)和EGFR蛋白(68.1%)在胃腺癌组织中的阳性表达率显著高于癌旁组织(P<0.01),两者均阳性的表达率为50.9%;在癌旁组织中HIF-1α蛋白不表达,EGFR蛋白阳性表达率为25.0%。 HIF-1α蛋白的阳性表达与T分期相关(P=0.014)。联合检测HIF-1α和EGFR蛋白两者均阳性表达与浸润深度及临床分期相关(P=0.006,P=0.023)。HIF-1α与EGFR蛋白表达之间有显著的正相关关系(r=0.331,P=0.000)。Kaplan-Meier生存分析结果显示,EGFR蛋白阳性表达的胃癌患者生存时间较阴性组明显缩短(29.6 vs 48.4个月,P<0.019);多因素Cox回归分析结果表明,EGFR作为独立因子可预测胃癌患者的不良预后。结论: HIF-1α、EGFR蛋白在胃腺癌组织中均呈高表达, 两者密切相关,在胃癌发生发展中有重要作用;EGFR可作为判断胃癌预后的重要指标。
[Key word]
[Abstract]
Objective:To investigate the expression of hypoxia-inducible factor-1α (HIF-1α) and epithelial growth factor receptor (EGFR) and their relationship to clinicopathological features and prognosis of gastric cancer. Methods: 116 cases of gastric carcinoma tissues and 20 cases of tumor-adjacent tissues, resected from July 2008 to July 2010 in the First Affiliated Hospital of Nanyang Medical College, were analyzed for the expression of HIF-1α and EGFR by immnohistochemical staining, as well as their correlation with clinicopathological factors and survival time. Results:The positive rates of HIF-1α (63.8%) and EGFR (68.1%) in cancer tissues were significantly higher than those in tumor-adjacent tissues (P<0.01). The rate for both HIF-1α+ and EGFR+ was 50.9%. The expression of HIF-1α was correlated with T staging (P=0.014), and the co-expression of HIF-1α+ and EGFR+ was correlated with invasion depth and TNM stage (P=0.006 and P=0.023). Spearman rank correlation analysis illustrated that there was a significant positive correlation between HIF-1α and EGFR (r=0.331,P=0.000). Kaplan-Meier survival analysis showed that the survival time of patients with positive EGFR expression was significantly shorter than those with negative expression (29.6 months vs 48.4 months,P<0.019). The multivariate Cox regression analysis demonstrated that EGFR positivity, as an independent factor, could predict poor prognosis for patients with gastric cancer. Conclusion: HIF-1α and EGFR were highly expressed in the tissues of gastric cancer; HIF-1α and EGFR were closely related with each other, and may play important roles in development and progression of gastric carcinoma. EGFR positivity may be used as important index to evaluate the prognosis of gastric carcinoma.
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[基金项目]
河南省医学科技攻关计划基金资助项目(No.201403213)