HIF-1α及Shp-2在结直肠癌组织中的表达及临床意义

Expression and Clinical Significance of HIF-1αand Shp-2 in Colorectal Carcinoma

目的:研究缺氧诱导因子-1α(hypoxia inducible factor 1 alpha,HIF-1α)和Shp-2(src homology protein tyrosine phosphatase-2)在结直肠癌组织中的表达,并分析这两种蛋白的表达情况与患者临床病理因素和预后之间的关系。方法:采用免疫组织化学法检测HIF-1α和Shp-2在124例患者结直肠癌组织中的表达,统计学分析HIF-1α和Shp-2的表达与临床病理参数及预后的关系,并同时分析这两种蛋白表达的相关性。结果:HIF-1α和Shp-2在结直肠癌中的阳性表达率分别为54.0%(67/124)和23.4%(29/124),两者表达呈负相关(r=-0.293,P=0.001)。HIF-α的表达阳性率在手术中发现远处转移及术后出现复发转移的患者中较高,Shp-2的表达阳性率在肿瘤浸润程度较深及术后出现复发转移的患者中较低(P<0.05)。Kaplan-Meier分析显示,HIF-1α表达阴性者预后好于表达阳性者(P=0.041),Shp-2表达阳性者预后好于表达阴性者(P=0.025);HIF-1α(-)Shp-2(+)组结直肠癌患者的预后显著优于HIF-1α(+)Shp-2(-)组(P=0.009)。结论:HIF-1α和Shp-2与结直肠癌患者预后及多个临床病理因素显著相关,提示这两种蛋白与结直肠癌的浸润转移密切相关,且可作为临床判断预后的标志物。

Objective： To investigate the expression of hypoxia induced factor-1α （ HIF-1α） and Src homology protein tyrosine phosphatase-2 （ Shp-2 ） in colorectal carcinoma （CRC）, and to explore the relationship of their expression with the survival and clinico- pathologic parameters of CRC patients. Methods： The expression of HIF-1α and Shp-2 in CRC specimens was detected by immunohis- tochemistry, and the corrlation between the expression of these two proteins and several clinicopathologic parameters of CRC patients was statistically analyzed. Results： The positive rates of HIF-1α and Shp-2 in CRC specimens were 54.0% （ 67/124 ） and 23.4% （ 29/ 124 ）, respectively. Negative correlation was observed between the expression of these two proteins （ r = -0.293, P = 0.001 ）. HIF-1α ex- pression was significantly correlated with distant metastasis at the time of surgery and also the recurrence and metastasis after surgery in CRC patients （ P 〈 0.05 ）. Shp-2 expression was significantly correlated with the depth of tumor invasion and post-surgery recur- rence and metastasis （ P 〈 0.05 ）. Moreover, Kaplan-Meier survival analyses revealed that the expression of low HIF-1α and high Shp-2 expression was significantly correlated with better survival of CRC patients （ P = 0.041 and 0.025, respectively ）. After combining these 2 markers, CRC patients with the expression pattern of HIF-1α （ - ） Shp-2 （ ＋ ） had longer survival time than those with HIF-1α （-） Shp-2 （ ＋ ）. Conclusion： The expression of H1F-1 α and Shp-2 was significantly correlated with several elinicopathologie characteristics and survival of CRC patients, suggested that these two proteins may play important roles in the invasion and metastasis process of CRC, and could be used as potential prognostic markers.