散发性结直肠癌组织中ezrin mRNA的表达及临床意义

Expression and clinical significance of ezrin mRNA in human primary sporadic colorectal carcinoma

目的研究散发性结直肠癌（SCRC）组织中ezrin mRNA的表达，探讨其在SCRC发生发展中的作用以及与ezrin蛋白表达部位、临床病理参数之间的关系。方法运用TaqMan实时逆转录-聚合酶链反应（real—time RT—PCR）技术检测132例SCRC患者的肿瘤组织及43例患者的癌旁正常组织中ezrinmRNA的表达；免疫组化法检测相应组织中ezrin蛋白的表达。结果SCRC组织中ezrinmRNA含量和ezrin蛋白表达阳性率均显著高于癌旁正常组织（P〈0．05）；转移组ezrinmRNA含量和ezrin蛋白表达阳性率均高于未转移组（P〈0．05）。转移组胞膜为主型ezrin蛋白表达阳性率（31．1％）显著高于未转移组（6．9％，P=0．0006）；转移组胞浆为主型ezrin蛋白表达阳性率（55．4％）与未转移组（63．8％）的差异无统计学意义（P〉0．05）；胞膜为主型组ezrinmRNA含量与胞浆为主型组的差异无统计学意义（P〉0．05）。年龄〈50岁组ezrinmRNA含量高于年龄≥50岁组（P=0．016）；右半结肠组胞膜为主型ezrin蛋白表达阳性率显著高于左半结肠和直肠（P=0．0003），左半结肠组胞浆为主型ezrin蛋白表达阳性率显著高于右半结肠和直肠（P=0．004）。ezrinmRNA、ezrin蛋自在SCRC中的表达与性别、肿瘤大小、侵袭程度、分化程度均无关（P〉0．05）。结论ezrinmRNA和ezrin蛋白表达的增高与SCRC的发生发展密切相关；ezrin蛋白表达从胞浆到胞膜的移位在肿瘤转移中可能起着重要作用；ezrinmRNA含量可能与患者年龄相关，ezrin表达部位可能与SCRC发生部位相关。ezrinmRNA、ezrin蛋白水平及表达部位可能成为临床判断SCRC预后的重要参考指标。

Objective To investigate the expression pattern of membrane-cytoskeleton linker ezrin mRNA in human sporadic colorectal carcinoma （SCRC） , and to evaluate the correlation of ezrin mRNA expression with carcinogenesis, progression and metastasis of SCRC. Methods TaqMan real-time reverse transcription polymerase chain reaction （ real-time RT-PCR） technique and immunohistochemical （ IHC ）. EnVision staining were used to detect the expression of ezrin mRNA and ezrin protein in 132 SCRC specimens and 43 adjacent normal colorectal mucosa specimens, including 74 cases with metastasis and 58 without. The correlation between the expression of ezrin mRNA and the process of carcinogenesis and metastasis in SCRC was analyzed, and the correlation between the location of ezrin expression and the clinicopathological parameters was also analyzed. Results The expression of ezrin mRNA and ezrin protein expression rate were significantly higher in SCRC than that in adjacent normal colorectal mucosa （P 〈 0.05）; which was also significantly higher in the metastatic group than that in the non-metastatic group （2. 3580 ± 0.5584 vs. 2.1129 ± 0.6625, P = 0.037 ;86.5% vs. 70.7%, P = 0. 026）. The rate of ezrin protein expression on the membrane was 31.1% in the metastatic group versus 6.9% in the non-metastatic group （ P 〈 0.001 ）, but ezrin mRNA expression was only slightly higher in the metastatic group （2. 2671 ± 0.5990） than that in the non-metastatic group （2. 2448 ±0. 6241 ）. No significant difference was found in cytoplasmic ezrin expression rate between the metastatic group （55.4%） and non-metastatic group （63. 8% ）. Ezrin mRNA expression was significantly higher in the group at age of 〈 50 years （2.5165 ± 0. 5755 ） than that at age of ≥ 50 years （2. 1762 ± 0. 6094, P = 0. 016）. The rate of ezrin protein expression on the membrane in the right colon was significantly higher than that in the left colon and rectum （ P = 0. 0003 ） , but rate of cytoplasmic ezrin protein expression in the left colon was higher than that in the right colon and rectum（ P = 0. 004 ）. No correlation was found between the expression level of ezrin mRNA and the age, sex, tumor size, location, differentiation and depth of invasion. Conclusion The expressions of ezrin mRNA and ezrin protein were closely correlated with the process of carcinogenesis, progression and metastasis in SCRC, and the ezrin protein expression is consistent with expression trend of ezrin mRNA. The switching of ezrin localization from the cytoplasm to the membrane may play an important role in metastasis. The expression of ezrin mRNA is correlated with patients＇age; membrane, and cytoplasmic ezrin expression is related to the tumor location. Ezrin may potentially become an important parameter in determining biological behavior of SCRC.