SEL1L基因在食管癌中的表达及意义

Expression of human Sel-1-like gene and its significance in esophageal cancer

目的探讨SEL1L(human Sel-1-like)mRNA及其蛋白在食管癌组织中的表达及其临床意义。方法应用免疫组织化学SP法检测90例手术切除的食管鳞状细胞癌、35例距癌灶边缘5 cm以上切缘的正常黏膜、60例癌旁黏膜及20例内窥镜活检的食管鳞状上皮不典型增生组织中SEL1L蛋白的表达;运用原位分子杂交技术检测上述癌组织、正常黏膜、癌旁黏膜中SEL1LmRNA的表达。结果(1)SEL1L mRNA在食管鳞状细胞癌的表达率为80.0%(72/90),较正常黏膜的14.3% (5/35)和癌旁黏膜的16.7%(10/60)高(P<0.01);SEL1LmRNA在有淋巴结转移组的表达阳性率为92.7%(38/41)比无淋巴结转移组69.4%(34/49)高(P<0.01)。(2)SEL1L蛋白在鳞状细胞癌的表达阳性率为87.8%(79/90),在鳞状上皮不典型增生中的表达阳性率为90.0%(18/20),分别较正常黏膜的14.3%(5/35)和癌旁黏膜的13.3%(8/60)高(P<0.01)。SEL1L蛋白表达与患者性别、年龄、肿瘤位置、大小、分化程度、浸润深度、淋巴结转移及临床分期均无明显相关性(P>0.05)。(3)食管鳞状细胞癌组织中SEL1LmRNA和SEL1L蛋白的表达呈明显正相关(P=0.492,P<0.01)。结论(1)SEL1L蛋白表达的调控主要在转录水平,SEL1L蛋白表达水平的升高主要是相应转录水平上调的结果。(2)SEL1L蛋白过表达可能是食管鳞状细胞癌发生的早期表现,SEL1L蛋白的检测可作为识别食管癌高风险患者的生物标记物。

Objective To study the expression of SEL1L （human Sel-1-like gene）mRNA and protein and its significance in esophageal cancer. Methods Immunohistochemical staining （S-P method ） for SEL1L protein was performed in 90 samples of esophageal squamous cell carcinoma, 35 samples of normal esophageal mucosa 5 cm away from the tumor, 60 samples of esophageal mucosa adjacent to the tumor and 20 samples of esophageal squamous dysplasia. In situ hybridization for SEL1L mRNA was also carried out in the esophageal carcinoma cases and normal esophageal mucosa distant from and adjacent to the tumor. Results The positive rate of SEL1 L mRNA was higher in esophageal carcinoma （ 80. 0%, 72/90）, as compared with that in normal esophageal mucosa distant from （ 14. 3% , 5/35 ） and adjacent to （ 16. 7%, 10/60） the tumor （P 〈 0. 01 ）. The positive rate of SEL1L mRNA in tumors with lymph node metastasis （92. 7%, 38/41 ） was higher than that in tumors without lymph node metastasis （69. 4%, 34/49） （P 〈 0.01）. On the other hand, the expression rate of SEL1L protein was higher in esophageal carcinoma （87.8% , 79/90） and esophageal dysplasia （90.0% , 18/20）, as compared with that in normal esophageal mucosadistant from （14.3%, 5/35） and adjacent to （13.3%, 8/60） the tumor （P〈0.01）. The expression of SEL1 L protein in esophageal cancer however did not correlate with age and sex of the patient, tumor location, tumor size, degree of differentiation, depth of tumor invasion, lymph node metastasis and tumor clinical stage （ P 〉 0. 05 ）. A positive correlation was found between the expression of SEL1 L mRNA and SEL1L protein （ r = 0. 492, P 〈 0. 01 ）. Conclusions SEL1L protein expression is regulated at the transcriptional level. The high SEL1L protein expression is mainly the result of increased transcription. Overexpression of SEL1L protein is likely an early event during the pathogenesis of esophageal squamous cell carcinoma. SEL1 L protein may serve as an important biomarker in identifying patients with higher risk of developing esophageal cancer.