直肠癌HIF-1α和COX-2的表达与新辅助放化疗敏感性的相关性

Relationship between the sensitivity of neoadjuvant chemoradiotherapy and the expression of HIF-1α and COX-2 in rectal cancer

目的:探讨直肠癌组织中HIF-1α和下游调控基因COX-2的表达与新辅助放化疗敏感性的相关性。方法:收集2008年4月至2013年3月行新辅助放化疗后行手术治疗的直肠癌患者45例,应用免疫组织化学方法检测新辅助放化疗前活检组织标本中HIF-1α和COX-2蛋白的表达,用改良Wheeler直肠癌消退分级(mRCRG)体系和T分期降期来评估新辅助放化疗的效果。结果:活检组织中HIF-1α低表达组有50.0%患者在放化疗后肿瘤消退达到mRCRG I级,高表达组仅有16.0%,两者差异有统计学意义(P<0.05)。活检组织中HIF-1α低表达组在放化疗后T分期降期率为70.0%,高表达组为32.0%,两者相比差异有统计学意义(P<0.05)。COX-2表达水平与mRCRG肿瘤消退等级及T分期降期无关(均P>0.05)。直肠癌组织中HIF-1α与COX-2表达呈低度正相关(r=0.36,P<0.05)。结论:直肠癌组织中HIF-1α表达水平与直肠癌新辅助放化疗疗效密切相关,可作为预测直肠癌新辅助放化疗的敏感性指标之一。

therapy and the expression of HIF-1alpha and its downstream gene COX-2 in rectal cancer.Methods： Between April 2008 and March 2013, 45 patients with histologically proven rectal cancer who underwent neoadjuvant chemoradiotherapy followed by surgery were investigated. Immunohistochemical assay was performed in pre-chemoradiotherapy specimens to determine the expression of HIF-1alpha and COX-2 protein. All cases were evaluated with modiifed Rectal Cancer Regression Grade （mRCRG） and T- level downstaging following neoad-juvant chemoradiotherapy.Results： The percent of achieving mRCRG I was higher in group of low HIF-1alpha expression than that of high HIF-1alpha expression after neoadjuvant chemoradiotherapy （50.0% vs 16.0%, P〈0.05）. The percentage of achieving T-level downstaging was also the same （70.0% vs 32.0%,P〈0.05）. The expression of COX-2 did not correlate with mRCRG and T-level downstaging in these patients （bothP〉0.05）. There was low positive correlation between the expression of HIF-1alpha and COX-2 in biopsy specimens of rectal cancer （r= 0.36,P〈0.05）.Conclusion： The expression of HIF-1alpha is associated with efficiency of neoadjuvant chemoradiation of rectal cancer. Therefore, it can be used as the sensitive predictor of neoadjuvant chemoradiation of rectal cancer.