结直肠癌中HSF1、SIRT1与MDR1蛋白表达的相关性及其临床病理意义

Correlation of HSF1, SIRT1 and MDR1 expression in colorectal cancer and its significance

目的探讨结直肠癌组织中热休克转录因子HSF1与SIRT1、MDR1蛋白表达的相关性及其临床病理意义。方法应用免疫组化和Western blot检测结直肠癌组织和正常结直肠黏膜组织中HSF1、SIRT1、MDR1的表达,分析三者之间的相关性及其与临床病理特征、预后的关系。结果(1)结直肠癌组织中HSF1、SIRT1、MDR1的表达水平高于正常结直肠黏膜组织,差异有显著性(P<0.05);(2)HSF1阳性组的结直肠癌中,MDR1的表达高于HSF1阴性组,差异有统计学意义(P<0.01),Spearman相关分析显示,HSF1与MDR1的表达呈正相关(r=0.478,P<0.01);(3)HSF1与SIRT1均阳性的结直肠癌组中MDR1的表达高于其他组,差异有显著性(P<0.01),Spearman相关分析显示,HSF1阳性组中MDR1的表达与SIRT1呈正相关(r=0.316,P<0.01);(4)HSF1、SIRT1的表达水平与肿瘤分化程度、淋巴结转移有相关性,且HSF1的表达与肿瘤的浸润深度相关;三者均是结直肠癌预后的独立危险因素。结论结直肠癌中HSF1与MDR1的表达有相关性,参与肿瘤多药耐药性;SIRT1可影响HSF1对MDR1的调控;HSF1、SIRT1的表达与肿瘤的生物学行为有关,三者可作为评估结直肠癌患者预后及个性化治疗的潜在分子标志物。

Purpose To investigate the correlation and clinical pathological significance of HSF1 with SIRT1 and MDR1 proteins expression in colorectal cancer tissues.Methods The expression of HSF1,SIRT1 and MDR1 in colorectal cancer tissues and normal tissues was detected by immunohistochemistry and Western blot.The correlation among the three,as well as its relationship with clinicopathological factors and prognosis was also analyzed.Results(1)The expressions of HSF1,SIRT1 and MDR1 in colorectal cancer tissues were higher than those in normal colorectal muxosa(P<0.05).(2)The expression of MDR1 in the colorectal cancer group with high expression of HSF1 was higher than that in those with low expression of HSF1(P<0.01).Spearmann correlation showed there were positive correlation between expression of HSF1 and MDR1(r=0.478,P<0.01).(3)The expression of MDR1 in colorectal cancer with high expression of HSF1 and SIRT1 was significantly higher than that in other groups(P<0.01).Spearmann correlation analysis showed the expression of MDR1 was positively correlated with SIRT1 in HSF1 positive group(r=0.316,P<0.01).(4)The expression of HSF1 and SIRT1 was correlated with the differentiation and lymph node metastasis,and the expression of HSF1 was correlated with the invasion,all of which were independent risk factors for prognosis of colorectal cancer.Conclusion The expression of HSF1 is correlated with MDR1 in colorectal cancer which may be involved in multidrug resistance.The expression of SIRT1 can affect the regulation of HSF1 on MDR1.The expression of HSF1 and SIRT1 is related to the biological behavior of colorectal cancer,which can be used as potential molecular markers to evaluate the prognosis and personalized treatment of colorectal cancer patients.