中文摘要：

目的 研究上皮膜蛋白2（epithelial membrane protein 2,EMP2）在多种人类肿瘤中的蛋白表达谱,并在小鼠乳腺癌模型中研究EMP2多肽疫苗的预防及治疗效果。方法 采用大样本组织芯片检测人体常见20种肿瘤中,EMP2在正常组织与相对应的肿瘤组织的表达。体外化学合成EMP2多肽,并与KLH蛋白偶联。于小鼠接瘤前后免疫Balb/c小鼠,ELISA法检测免疫后小鼠抗EMP2抗体的血清效价。建立4T1细胞荷瘤小鼠预防及治疗模型,随机分为生理盐水组、单纯KLH组、单纯佐剂组、KLHEMP2多肽组,每组各10只。观察KLH-EMP2多肽疫苗对乳腺癌模型的成瘤率、肿瘤生长情况、体重及生存期的影响。结果 与相应正常组织比较,EMP2在乳腺癌、子宫内膜癌、卵巢癌、宫颈癌、膀胱癌、甲状腺癌等肿瘤中明显高表达。而在胰腺癌、前列腺癌及脑部肿瘤中呈低表达或阴性表达。KLH-EMP2多肽免疫小鼠后,构建小鼠乳腺癌4T1荷瘤模型,对照组成瘤率为100%,佐剂组及单纯KLH组成瘤率分别为100%,100%,KLH-EMP2多肽组成瘤率为70%。较之对照组、佐剂组及单纯KLH组,KLHEMP2多肽组可明显抑制4T1肿瘤生长（P=0.009）。同时,延长荷瘤小鼠生存时间（P=0.001）,同时,免疫对小鼠的体重无明显变化（P=0.58）。在4T1肿瘤治疗模型中,KLH-EMP2多肽治疗可明显抑制4T1肿瘤生长（P=0.001）和大小（P=0.006）。同时,延长4T1荷瘤小鼠生存期（P=0.03）。结论EMP2在乳腺癌中呈高表达,EMP2多肽疫苗具有明显的乳腺癌预防及治疗作用。

英文摘要：

Objective To investigate the protein expression profile of epithelial membrane protein 2 （EMP2） in a variety of human cancers, and to determine the preventive and therapeutic effect of EMP2 polypeptide vaccine in mouse breast cancer model. Methods The expression of EMP2 in normal tissues and corresponding tumor tissues was detected by tissue microarray. EMP2 polypeptide was synthesized chemically in vitro, and then coupled with protein keyhole limpet hemocyanin （KLH）. The serum titer of anti-EMP2 antibody was detected by ELISA in the immunized mice. The prevention and treatment of tumor bearing mice of breast cancer 4T1 cells were randomly divided into saline group, KLH group, simple adjuvant group, and KLH-EMP2 group, with I0 mice in each group. The mice were immunized with KLH-EMP2 polypeptide vaccine or other corresponding agents before the establishment of mouse 4T1 breast cancer tumor. Tumorigenesis, tumor growth, weight and survival were observed to determine the effect of KLH-EMP2 peptide vaccine on breast cancer model. Results Compared with the normal tissues, EMP2 was significantly higherin breast cancer, endometrial cancer, ovarian cancer, cervical cancer, bladder cancer, thyroid cancer and other tumors, but it was not or mildly expressed in pancreatic cancer, prostate cancer and brain tumors. The tumor formation rate was 100% for the saline group, KLH group, and simple adjuvant group, but only 70% for the KLH-EMP2 group. KLH-EMP2 peptide resulted in significant inhibitory effect on tumor growth （P = 0. 009 ）, prolonged the survival of xenograft mice （ P = 0.001 ）, but had no effect on the body weight （ P = 0. 58） when compared with the other 3 groups. In the 4T1 tumor treatment model, KLH-EMP2 polypeptide significantly inhibited 4T1 tumor growth （ P = 0. 001 ） and weight （ P = 0. 006 ）, and at the same time, prolonged the survival of 4T1 tumor bearing mice （P = 0.03 ）. Conclusion EMP2 is highly expressed in breast cancer, and EMF2 peptide vaccine has obvious preventive a