青海地区乳腺癌发病特点及HIF-2α、CA9、CA12在乳腺癌发病机制中的探索研究
发布时间：2018-12-29 17:51
【摘要】：目的:乳腺癌是全世界女性最常见的恶性肿瘤,在我国发病率已居女性恶性肿瘤的首位,且呈上升趋势。低氧在恶性肿瘤的发生发展过程中起到极为关键的作用,其中涉及低氧诱导因子(Hypoxia inducible factor,HIF)家族和碳酸酐酶(Carbonic anhydrase,CA)家族的调控。低氧诱导因子家族在低氧条件下可触发多种导致肿瘤进展的基因的表达,直接或间接地促进肿瘤进展的过程。碳酸酐酶是肿瘤微环境p H调节的关键因子。本课题拟从流行病学、临床病理特征、分子机制角度研究青海高原地区女性乳腺癌的发病特点、临床病理特征,并进一步探索分析HIF-2α、CA9、CA12在乳腺癌侵袭、转移过程中的作用。方法：1.统计青海大学附属医院2001-2010年10年的全部恶性肿瘤病例资料,回顾性分析青海地区恶性肿瘤的流行病学特点,特别是乳腺癌的发病资料。2.统计青海大学附属医院2001-2012年收治的汉族、藏族、回族共259例乳腺癌病例,回顾性分析比较三个民族乳腺癌的临床及病理学特点。3.收集94例乳腺癌患者总结其临床资料。使用免疫组化方法检测HIF-2α、CA9、CA12的表达,并将其与临床病理特点建立相关性。使用慢病毒载体构建Si RNA干扰质粒以沉默HIF-2α,培养并转染MCF-7细胞,使用JNK抑制剂SP600125处理后在常氧及低氧条件下检测MCF-7细胞及HIF-2α沉默细胞HIF-2α、CA9、CA12的表达。结果：1.男性主要的恶性肿瘤是胃癌、肺癌、肝癌、结直肠癌、食管癌,女性最常见的恶性肿瘤是胃癌、肺癌、乳腺癌、宫颈癌、结直肠癌。恶性肿瘤在不同海拔地区每10万人口年新发病例约为47.39、31.21、10.91(P0.001),有统计学意义。乳腺癌就诊数较少,在少数民族中呈散发。2.回族、藏族乳腺癌患者35岁前发病比例较汉族高;藏族、汉族在36-50岁年龄段较常见,比回族比例高。汉族乳腺癌患者中生育次数少者较其它民族高。3.HIF-2α在乳腺癌T2及Ⅱ期中高表达(P0.05),CA12在Ⅱ期中高表达(P0.05),CA9、CA12的表达一致(R=0.376,P=0.0001),HIF-2α表达与CA9(P=0.21)、CA12(P=0.27)无相关性。HIF-2α在乳腺癌MCF-7细胞低氧条件下表达增强。在HIF-2α沉默细胞中CA9、CA12也有表达。JNK信号通路抑制剂SP600125可抑制HIF-2α表达,并抑制乳腺癌细胞的侵袭、粘附能力,但对CA9、CA12影响较小。结论：1.青海地区肿瘤发病呈递增趋势,发病情况与全国情况不一致;青海各民族恶性肿瘤的发生部位不同,均以消化道肿瘤常见,发病情况各异;随海拔的升高,除撒拉族外,各民族恶性肿瘤发病下降;乳腺癌呈散发特点,有增高趋势。2.青海地区乳腺癌的发病特点、病理特征及分子分型在各民族间无明显差异;生育次数少对汉族乳腺癌的发生有一定影响。3.HIF-2α、CA9、CA12是乳腺癌中重要的低氧调节因子,在低氧微环境中对乳腺癌的进展发挥作用,JNK信号通路参与乳腺癌的侵袭及转移。CA9、CA12的上游调控并非HIF-2α起主导作用,推测其受HIF-1α等其它低氧相关基因调控。
[Abstract]:Objective: breast cancer is the most common malignant tumor in women in the world. Hypoxia plays an important role in the development of malignant tumors, including the regulation of hypoxia inducible factor (Hypoxia inducible factor,HIF) family and carbonic anhydrase (Carbonic anhydrase,CA) family. Hypoxia inducible factor family can trigger the expression of many genes that lead to tumor progression directly or indirectly. Carbonic anhydrase (carbonic anhydrase) is a key factor in the regulation of pH in tumor microenvironment. This study aims to study the clinical and pathological characteristics of female breast cancer in Qinghai Plateau from the perspectives of epidemiology, clinicopathological features and molecular mechanisms, and to further explore the invasion of HIF-2 伪 and CA9,CA12 in breast cancer. The role of the transfer process. Method 1: 1. The data of all malignant tumor cases in the affiliated Hospital of Qinghai University from 2001 to 2010 were analyzed retrospectively. The epidemiological characteristics of malignant tumors, especially the incidence of breast cancer, were analyzed retrospectively. 2. A total of 259 cases of breast cancer from Han, Tibetan and Hui nationalities admitted in the affiliated Hospital of Qinghai University from 2001 to 2012 were retrospectively analyzed and compared with the clinical and pathological features of breast cancer in the three nationalities. 3. The clinical data of 94 patients with breast cancer were summarized. Immunohistochemical method was used to detect the expression of HIF-2 伪 and CA9,CA12, and to establish a correlation with clinicopathological features. Si RNA interference plasmid was constructed with lentivirus vector to silence HIF-2 伪, and MCF-7 cells were cultured and transfected with JNK inhibitor SP600125. MCF-7 cells and HIF-2 伪 silencing cells HIF-2 伪, CA9, were detected under normoxic and hypoxic conditions. Expression of CA12. Results: 1. The main malignancies in men are gastric cancer, lung cancer, liver cancer, colorectal cancer, esophageal cancer, and the most common malignant tumors in women are gastric cancer, lung cancer, breast cancer, cervical cancer, colorectal cancer. The number of new cases of malignant tumor per year of 100000 population at different elevations was about 47.3931.21 / 10.91 (P0. 001), which was statistically significant. The number of breast cancer visits is small and sporadic among ethnic minorities. 2. 2%. The incidence rate of breast cancer in Hui nationality and Tibetan nationality was higher than that in Han nationality before 35 years old, while it was more common in Tibetan and Han nationality at the age of 36 to 50 years, higher than that in Hui nationality. The expression of 3.HIF-2 伪 in T2 and 鈪，
本文编号：2395168
[Abstract]:Objective: breast cancer is the most common malignant tumor in women in the world. Hypoxia plays an important role in the development of malignant tumors, including the regulation of hypoxia inducible factor (Hypoxia inducible factor,HIF) family and carbonic anhydrase (Carbonic anhydrase,CA) family. Hypoxia inducible factor family can trigger the expression of many genes that lead to tumor progression directly or indirectly. Carbonic anhydrase (carbonic anhydrase) is a key factor in the regulation of pH in tumor microenvironment. This study aims to study the clinical and pathological characteristics of female breast cancer in Qinghai Plateau from the perspectives of epidemiology, clinicopathological features and molecular mechanisms, and to further explore the invasion of HIF-2 伪 and CA9,CA12 in breast cancer. The role of the transfer process. Method 1: 1. The data of all malignant tumor cases in the affiliated Hospital of Qinghai University from 2001 to 2010 were analyzed retrospectively. The epidemiological characteristics of malignant tumors, especially the incidence of breast cancer, were analyzed retrospectively. 2. A total of 259 cases of breast cancer from Han, Tibetan and Hui nationalities admitted in the affiliated Hospital of Qinghai University from 2001 to 2012 were retrospectively analyzed and compared with the clinical and pathological features of breast cancer in the three nationalities. 3. The clinical data of 94 patients with breast cancer were summarized. Immunohistochemical method was used to detect the expression of HIF-2 伪 and CA9,CA12, and to establish a correlation with clinicopathological features. Si RNA interference plasmid was constructed with lentivirus vector to silence HIF-2 伪, and MCF-7 cells were cultured and transfected with JNK inhibitor SP600125. MCF-7 cells and HIF-2 伪 silencing cells HIF-2 伪, CA9, were detected under normoxic and hypoxic conditions. Expression of CA12. Results: 1. The main malignancies in men are gastric cancer, lung cancer, liver cancer, colorectal cancer, esophageal cancer, and the most common malignant tumors in women are gastric cancer, lung cancer, breast cancer, cervical cancer, colorectal cancer. The number of new cases of malignant tumor per year of 100000 population at different elevations was about 47.3931.21 / 10.91 (P0. 001), which was statistically significant. The number of breast cancer visits is small and sporadic among ethnic minorities. 2. 2%. The incidence rate of breast cancer in Hui nationality and Tibetan nationality was higher than that in Han nationality before 35 years old, while it was more common in Tibetan and Han nationality at the age of 36 to 50 years, higher than that in Hui nationality. The expression of 3.HIF-2 伪 in T2 and 鈪，
本文编号：2395168
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