ARHI和BECN1在乳腺癌中的表达及意义

发布时间：2018-06-25 19:30

本文选题：ARHI + BECN1　；参考：《大连医科大学》2017年硕士论文

【摘要】：背景:乳腺癌是一种临床常见的恶性肿瘤,威胁世界女性健康,近年来其发病率持续升高,并且发病趋势逐渐年轻化。癌基因和抑癌基因均存在于机体正常细胞内,正常情况下,它们以正负信号“平衡状态”调节细胞的增殖分化,当内在、外界因素使得抑癌基因失活或癌基因激活后,这种“平衡状态”被打破,从而导致正常细胞向癌细胞的转化。乳腺癌的发生、发展是多种基因变异累积的病变过程,抑癌基因的失活在乳腺癌的演变过程中发挥重要作用。ARHI(Aplasia Ras homolog memberⅠ),又名NOEY2或DIRAS3,属小G蛋白Ras超家族,是该家族第一个被报道的抑癌基因,在肿瘤的生长侵袭和自噬过程中起重要作用。BECN1是酵母中Atg6的同源物,可与Ⅲ型PI3K及Vps34相结合启动自噬,和ARHI一样,与肿瘤和自噬也有密不可分的联系。既往研究表明,ARHI和BECN1在肿瘤中均表现为抑癌效应,在乳腺癌、卵巢癌、胰腺癌等多种恶性肿瘤中表达下调/缺失,但针对二者之间相关性的研究尚不多见。目的:通过检测ARHI和BECN1在乳腺良性病变、乳腺癌及相应癌旁组织中的表达水平,分析二者与乳腺癌临床病理参数之间的关系,探讨ARHI和BECN1在乳腺癌中的临床意义;通过分析二者在乳腺癌各分子亚型间的表达差异,为临床筛选高侵袭性乳腺癌提供理论依据,从而指导临床治疗。方法:收集2015年01月~2016年12月于大连医科大学第二临床学院、大连市中心医院接受手术治疗的组织蜡块标本123例,其中乳腺良性病变24例、乳腺癌84例及相应癌旁组织15例。应用免疫组织化学方法(SP法)检测乳腺良性病变、乳腺癌及相应癌旁组织中ARHI、BECN1的表达情况;应用统计学方法分析二者与乳腺癌临床病理参数的关系及它们在乳腺癌中的表达相关性。结果:1、ARHI在乳腺良性病变、乳腺癌、癌旁组织中的阳性表达率分别为87.5%(21/24)、46.4%(39/84)和93.3%(14/15),在乳腺癌组织中的阳性表达率明显低于另两组,差异具有显著统计学意义(P0.01)。ARHI在乳腺癌中的表达与癌组织的病理分化程度、淋巴结转移情况以及PR(孕激素受体)表达情况相关(P0.05),而与患者的发病年龄、月经状态、是否有肿瘤家族史、临床分期、肿瘤大小、是否存在脉管癌栓或神经侵犯、ER、Her-2及CK5/6无明显相关性(P0.05)。2、BECN1在乳腺良性病变、乳腺癌、癌旁组织中的阳性表达率分别为91.7%(22/24)、51.2%(43/84)和86.7%(13/15),在乳腺癌组织中的阳性表达率明显低于另两组,差异有统计学意义(P0.05)。BECN1在乳腺癌中的表达与临床分期、病理分化程度、淋巴结转移情况、是否有脉管癌栓及Her-2表达情况相关(P0.05),而与发病年龄、月经状态、是否有肿瘤家族史、肿瘤大小、是否存在神经侵犯、ER、PR及CK5/6无相关性(P0.05)。3、在84例乳腺癌组织中,ARHI与BECN1的表达呈正相关(相关系数r=0.288,P=0.008)。4、ARHI和BECN1在Luminal A与Her-2扩增型乳腺癌中的阳性表达率高且接近,其次为Luminal B型,在三阴性乳腺癌中的阳性表达率均最低。在乳腺癌各分子亚型中,ARHI的表达差异具有统计学意义(x2=22.040,P=0.000),而BECN1的表达差异无统计学意义(x2=6.330,P=0.097)。结论:1、ARHI和BECN1在乳腺癌中低表达,阳性表达率明显低于癌旁组织和乳腺良性病变。2、ARHI和BECN1在Luminal A与Her-2扩增型乳腺癌中的阳性表达率高且接近,在三阴性乳腺癌中表达率均最低;ARHI在乳腺癌各分子亚型中的表达差异有统计学意义。3、ARHI和BECN1在乳腺癌中的表达呈正相关。4、在乳腺癌中,ARHI与BECN1的联合检测有助于评估肿瘤恶性程度、判断预后、指导临床治疗等。
[Abstract]:Background: breast cancer is a common malignant tumor which threatens the health of women in the world. In recent years, the incidence of breast cancer has been increasing, and the incidence trend is gradually younger. The oncogene and tumor suppressor genes are all in the normal cells of the body. Under normal circumstances, they regulate cell proliferation and differentiation with positive and negative signals "balance", when inherent, After external factors make the tumor suppressor gene inactivation or oncogene activation, this "balance state" is broken, which leads to the transformation of normal cells to cancer cells. The development of breast cancer is the accumulation of various gene mutations, and the inactivation of the tumor suppressor gene plays an important role in the evolution process of breast cancer.ARHI (Aplasia Ras homolo). G member I), also known as NOEY2 or DIRAS3, is a small G protein Ras superfamily, and is the first reported tumor suppressor gene in the family. It plays an important role in the growth invasion and autophagy of the tumor..BECN1 is the homology of Atg6 in yeast. It can be combined with type III PI3K and Vps34 to start autophagy, like ARHI, and also inseparable from tumor and autophagy. Previous studies have shown that both ARHI and BECN1 are tumor suppressor effects in the tumor, and are down-regulated and deleted in many malignant tumors such as breast, ovarian and pancreatic cancer. However, there are few studies on the correlation between the two. Objective: to detect the expression of ARHI and BECN1 in breast benign lesions, breast cancer and corresponding para cancerous tissues To analyze the relationship between the two and the clinicopathological parameters of breast cancer, to explore the clinical significance of ARHI and BECN1 in breast cancer, and to provide a theoretical basis for the clinical screening of high invasive breast cancer by analyzing the differences in the expression of the two subtypes of the breast cancer molecules, and to guide the clinical treatment. Methods: to collect the December 2015 ~2016 year in 2015. The Second Clinical College of Dalian Medical University and Dalian central hospital received surgical treatment of 123 tissue paraffin specimens, including 24 benign breast lesions, 84 breast cancer and 15 corresponding para cancerous tissues. The expression of ARHI and BECN1 in breast benign lesions, breast cancer and corresponding para cancerous tissues was detected by SP method. The relationship between the two and the clinicopathological parameters of breast cancer and their correlation in breast cancer were statistically analyzed. Results: 1, the positive expression rate of ARHI in benign breast lesions, breast cancer and para cancerous tissues was 87.5% (21/24), 46.4% (39/84) and 93.3% (14 /15), and the positive expression rate in breast cancer tissues was significantly lower than that of the other two. The difference has significant statistical significance (P0.01) the expression of.ARHI in breast cancer is related to the degree of pathological differentiation, lymph node metastasis and the expression of PR (progestin receptor) (P0.05), and the age of the patients, the state of menstruation, the family history of the tumor, the clinical stage, the size of the tumor, and whether there is a vascular tumor thrombus or whether there is a vascular tumor thrombus or whether or not. There was no significant correlation between ER, Her-2 and CK5/6 (P0.05).2. The positive expression rate of BECN1 in benign breast lesions, breast cancer and adjacent tissues was 91.7% (22/24), 51.2% (43/84) and 86.7% (13/15), and the positive expression rate in breast cancer tissues was significantly lower than that in the other two groups, and the difference was statistically significant (P0.05).BECN1 in breast cancer The clinical stage, the degree of pathological differentiation, lymph node metastasis, the correlation of the vascular tumor thrombus and the expression of Her-2 (P0.05), and the age, menstruation, the family history of the tumor, the size of the tumor, the existence of nerve invasion, the ER, PR and CK5/6 non correlation (P0.05).3, and the expression of ARHI and BECN1 in 84 cases of breast cancer. The positive expression rate of correlation coefficient r=0.288, P=0.008).4, ARHI and BECN1 in Luminal A and Her-2 amplification breast cancer is high and close, followed by Luminal B type, and the positive expression rate in three negative breast cancers is the lowest. There was no statistical significance (x2=6.330, P=0.097). Conclusion: 1, ARHI and BECN1 were low expression in breast cancer, and the positive expression rate was significantly lower than that of para cancerous tissues and benign breast lesions. The positive expression rate of ARHI and BECN1 in Luminal A and Her-2 expanded breast cancer was high and close, and the expression rate in three negative breast cancers was the lowest; ARHI in breast cancer. The expression differences in the subtypes of each molecule are statistically significant.3, the expression of ARHI and BECN1 in breast cancer is positively correlated with.4. In breast cancer, the combined detection of ARHI and BECN1 can help to evaluate the malignancy of the tumor, judge the prognosis, and guide the clinical treatment.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9

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