LETM1蛋白过表达在三阴性乳腺癌中的预后评估意义

发布时间：2018-04-20 02:40

本文选题：三阴性乳腺癌 + LETM1蛋白　；参考：《吉林大学》2016年硕士论文

【摘要】：研究背景:乳腺癌是目前中国女性最常见的恶性肿瘤,也是全世界肿瘤致死的首要原因。三阴性乳腺癌是指免疫组织化学染色显示雌激素受体、孕激素受体和人类表皮生长因子受体2均为阴性的一种特殊的乳腺癌。三阴性乳腺癌约占乳腺癌的12-17%,比非三阴性乳腺癌的侵袭性更强、复发转移更早,在转移性乳腺癌中生存率更低,预后更差。此外,由于三阴性乳腺癌对内分泌治无反应,目前治疗主要以手术为主,辅以全身性化疗,但该肿瘤异质性大,临床预后差,寻找有效的分子指标和治疗靶点已迫在眉睫。LETM1蛋白是一种在人类及酵母中都较为保守的线粒体内膜蛋白,它能减少线粒体的生成及ATP的产生。其表达水平的异常能诱发线粒体功能的紊乱,从而导致包括肿瘤等人类多种疾病的发生。在人类众多恶性肿瘤中都发现LETM1蛋白表达水平显著升高,但是LETM1过表达在三阴性乳腺癌中的临床病理特点和预后意义仍不清楚。本研究旨在探讨LETM1蛋白过表达在三阴性乳腺癌中的临床预后评估意义。材料与方法:选取组织标本共214例,其中包括107例三阴性乳腺癌,42例导管内原位癌,65例癌旁正常组织。首先,应用细胞免疫荧光染色检测方法分析LETM1蛋白在MCF-7乳腺癌细胞中的定位情况。然后采用免疫蛋白印迹方法在三阴性乳腺癌组织中对LETM1蛋白进行相对定量,验证LETM1蛋白在三阴性乳腺癌中是否存在过表达。最后,采用免疫组织化学方法检测LETM1蛋白在三阴性乳腺癌、导管内原位癌及正常组织中的表达情况,并分析其蛋白表达在三阴性乳腺癌中的临床病理意义。结果:1.免疫荧光结果显示,LETM1蛋白主要定位于细胞浆,这与本研究的免疫组化染色结果定位一致。2.免疫蛋白印迹结果表明,与癌旁正常组织相比,三阴性乳腺癌组织中LETM1蛋白表达增加。3.免疫组化结果显示,LETM1蛋白在三阴性乳腺癌的阳性率为85.0%(91/107),比导管内原位癌(64.3%,27/42)及癌旁正常组织(29.2%,19/65)显著增强(P0.001)。同样,LETM1蛋白在三阴性乳腺癌的强阳性率为69.2%(74/107)也显著高于导管内原位癌(35.7%,15/42)及癌旁正常组织(12.3%,8/65)(P0.001)。更重要的是,LETM1蛋白表达在导管内原位癌的阳性率及强阳性率均较癌旁正常组织高,且差异有显著性(P0.001)。此外,LETM1蛋白强阳性表达率在病理学分级Ⅱ级(27/37,73.0%)和Ⅲ级(34/43,79.1%)中与Ⅰ级(13/27,48.1%)相比均有显著性差异(P均=0.020);在伴有淋巴结转移的三阴性乳腺癌组织中LETM1强阳性表达率为82.3%,与无淋巴结转移的51.1%相比有显著性差异(P=0.001);同样,LETM1蛋白强阳性表达率在晚期三阴性乳腺癌组织中(Ⅲ-Ⅳ期)为88.4%,而在早期三阴性乳腺癌(Ⅰ-Ⅱ期)仅为56.3%(36/64)(P=0.000)。但LETM1蛋白过表达与年龄、绝经状态和组织大小等无明显相关性(P均0.05)。此外,生存期分析显示,LETM1蛋白过表达的三阴性乳腺癌患者的10年总生存期及无病生存期均明显低于LETM1蛋白低表达的患者(P=0.000)。结论:LETM1蛋白过表达与三阴性乳腺癌发生发展及预后密切相关。LETM1蛋白高表达有望成为三阴性乳腺癌患者一个潜在生物学指标及治疗靶点。
[Abstract]:Background: breast cancer is the most common malignant tumor in Chinese women and the leading cause of death in the world. Three negative breast cancer is a special kind of breast cancer with immunohistochemical staining of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Three negative breast cancer accounts for about breast cancer. The 12-17% of adenocarcinoma is more aggressive than non three negative breast cancer, the recurrence is earlier, the survival rate is lower in metastatic breast cancer, and the prognosis is worse. In addition, because three negative breast cancer has no response to the endocrine treatment, the treatment is mainly based on surgery, supplemented by systemic therapy, but the tumor heterogeneity is large, the clinical prognosis is poor, looking for effective prognosis. Molecular targets and therapeutic targets have been imminent as an imminent.LETM1 protein, a kind of mitochondrial membrane protein, which is more conservative in human and yeast. It can reduce the formation of mitochondria and the production of ATP. The abnormal expression level can induce the dysfunction of mitochondrial function, which leads to the occurrence of many human diseases, including swelling, and so on. LETM1 protein expression levels were significantly increased in malignant tumors, but the clinicopathological features and prognostic significance of LETM1 overexpression in three negative breast cancers were still unclear. The purpose of this study was to explore the clinical prognostic significance of LETM1 protein overexpression in three negative breast cancers. Materials and methods: 214 cases of tissue specimens were selected. 107 cases of three negative breast cancer, 42 cases of intraductal carcinoma in situ, 65 cases of normal para cancer tissue. First, the localization of LETM1 protein in MCF-7 breast cancer cells was analyzed by cell immunofluorescence staining, and the relative quantification of LETM1 protein in three negative breast cancer tissues by immunoblotting was used to verify the LETM1 eggs Whether there is overexpression in three negative breast cancer. Finally, immunohistochemistry was used to detect the expression of LETM1 protein in three negative breast cancer, intraductal carcinoma in situ and normal tissues, and analyzed the clinicopathological significance of protein expression in three negative breast cancer. Results: 1. immunofluorescence results showed that LETM1 protein was the main protein. Located in the cytoplasm, this was consistent with the immunohistochemical staining results of this study. The results of.2. immunoblotting showed that the expression of LETM1 protein in three negative breast cancer tissues increased by.3. immunohistochemical staining, and the positive rate of LETM1 protein in three negative breast cancer was 85% (91/107), compared with that of intraductal carcinoma in situ (64.). 3%, 27/42) and paracancerous normal tissues (29.2%, 19/65) were significantly enhanced (P0.001). Similarly, the strong positive rate of LETM1 protein in three negative breast cancers was 69.2% (74/107) and was significantly higher than that of intraductal carcinoma in situ (35.7%, 15/42) and normal tissue adjacent to the carcinoma (12.3%, 8/65) (P0.001). More importantly, the positive rate and strong positive rate of LETM1 protein expression in the ductal carcinoma in situ were more important. In addition, the strong positive expression rate of LETM1 protein was significantly different from grade I (13/27,48.1%) in grade II (27/37,73.0%) and grade III (P) in pathological grade II (27/37,73.0%) and grade III (P =0.020). The strong positive expression of LETM1 in three negative breast cancer tissues accompanied by lymph node metastasis was found. The rate of 82.3% was significantly different from that of 51.1% without lymph node metastasis (P=0.001). Similarly, the strong positive expression rate of LETM1 protein in advanced three negative breast cancer tissues (stage III - IV) was 88.4%, while in the early three negative breast cancer (stage I - II) was only 56.3% (36/64) (P=0.000). But the overexpression of LETM1 protein was associated with age, menopause and tissue size. There was no significant correlation (P 0.05). In addition, the survival time analysis showed that the 10 year total and disease-free survival of the three negative breast cancer patients with over expression of LETM1 protein were significantly lower than those of the low expression of LETM1 protein (P=0.000). Conclusion: the overexpression of LETM1 protein is closely related to the development and prognosis of three negative breast cancer, which is closely related to the high expression of the protein. Da is expected to be a potential biological indicator and therapeutic target for three negative breast cancer patients.

【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R737.9

【相似文献】