青海地區(qū)乳腺癌發(fā)病特點(diǎn)及HIF-2α、CA9、CA12在乳腺癌發(fā)病機(jī)制中的探索研究
發(fā)布時(shí)間：2018-12-29 17:51
【摘要】：目的:乳腺癌是全世界女性最常見(jiàn)的惡性腫瘤,在我國(guó)發(fā)病率已居女性惡性腫瘤的首位,且呈上升趨勢(shì)。低氧在惡性腫瘤的發(fā)生發(fā)展過(guò)程中起到極為關(guān)鍵的作用,其中涉及低氧誘導(dǎo)因子(Hypoxia inducible factor,HIF)家族和碳酸酐酶(Carbonic anhydrase,CA)家族的調(diào)控。低氧誘導(dǎo)因子家族在低氧條件下可觸發(fā)多種導(dǎo)致腫瘤進(jìn)展的基因的表達(dá),直接或間接地促進(jìn)腫瘤進(jìn)展的過(guò)程。碳酸酐酶是腫瘤微環(huán)境p H調(diào)節(jié)的關(guān)鍵因子。本課題擬從流行病學(xué)、臨床病理特征、分子機(jī)制角度研究青海高原地區(qū)女性乳腺癌的發(fā)病特點(diǎn)、臨床病理特征,并進(jìn)一步探索分析HIF-2α、CA9、CA12在乳腺癌侵襲、轉(zhuǎn)移過(guò)程中的作用。方法：1.統(tǒng)計(jì)青海大學(xué)附屬醫(yī)院2001-2010年10年的全部惡性腫瘤病例資料,回顧性分析青海地區(qū)惡性腫瘤的流行病學(xué)特點(diǎn),特別是乳腺癌的發(fā)病資料。2.統(tǒng)計(jì)青海大學(xué)附屬醫(yī)院2001-2012年收治的漢族、藏族、回族共259例乳腺癌病例,回顧性分析比較三個(gè)民族乳腺癌的臨床及病理學(xué)特點(diǎn)。3.收集94例乳腺癌患者總結(jié)其臨床資料。使用免疫組化方法檢測(cè)HIF-2α、CA9、CA12的表達(dá),并將其與臨床病理特點(diǎn)建立相關(guān)性。使用慢病毒載體構(gòu)建Si RNA干擾質(zhì)粒以沉默HIF-2α,培養(yǎng)并轉(zhuǎn)染MCF-7細(xì)胞,使用JNK抑制劑SP600125處理后在常氧及低氧條件下檢測(cè)MCF-7細(xì)胞及HIF-2α沉默細(xì)胞HIF-2α、CA9、CA12的表達(dá)。結(jié)果：1.男性主要的惡性腫瘤是胃癌、肺癌、肝癌、結(jié)直腸癌、食管癌,女性最常見(jiàn)的惡性腫瘤是胃癌、肺癌、乳腺癌、宮頸癌、結(jié)直腸癌。惡性腫瘤在不同海拔地區(qū)每10萬(wàn)人口年新發(fā)病例約為47.39、31.21、10.91(P0.001),有統(tǒng)計(jì)學(xué)意義。乳腺癌就診數(shù)較少,在少數(shù)民族中呈散發(fā)。2.回族、藏族乳腺癌患者35歲前發(fā)病比例較漢族高;藏族、漢族在36-50歲年齡段較常見(jiàn),比回族比例高。漢族乳腺癌患者中生育次數(shù)少者較其它民族高。3.HIF-2α在乳腺癌T2及Ⅱ期中高表達(dá)(P0.05),CA12在Ⅱ期中高表達(dá)(P0.05),CA9、CA12的表達(dá)一致(R=0.376,P=0.0001),HIF-2α表達(dá)與CA9(P=0.21)、CA12(P=0.27)無(wú)相關(guān)性。HIF-2α在乳腺癌MCF-7細(xì)胞低氧條件下表達(dá)增強(qiáng)。在HIF-2α沉默細(xì)胞中CA9、CA12也有表達(dá)。JNK信號(hào)通路抑制劑SP600125可抑制HIF-2α表達(dá),并抑制乳腺癌細(xì)胞的侵襲、粘附能力,但對(duì)CA9、CA12影響較小。結(jié)論：1.青海地區(qū)腫瘤發(fā)病呈遞增趨勢(shì),發(fā)病情況與全國(guó)情況不一致;青海各民族惡性腫瘤的發(fā)生部位不同,均以消化道腫瘤常見(jiàn),發(fā)病情況各異;隨海拔的升高,除撒拉族外,各民族惡性腫瘤發(fā)病下降;乳腺癌呈散發(fā)特點(diǎn),有增高趨勢(shì)。2.青海地區(qū)乳腺癌的發(fā)病特點(diǎn)、病理特征及分子分型在各民族間無(wú)明顯差異;生育次數(shù)少對(duì)漢族乳腺癌的發(fā)生有一定影響。3.HIF-2α、CA9、CA12是乳腺癌中重要的低氧調(diào)節(jié)因子,在低氧微環(huán)境中對(duì)乳腺癌的進(jìn)展發(fā)揮作用,JNK信號(hào)通路參與乳腺癌的侵襲及轉(zhuǎn)移。CA9、CA12的上游調(diào)控并非HIF-2α起主導(dǎo)作用,推測(cè)其受HIF-1α等其它低氧相關(guān)基因調(diào)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 偽 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 偽 and CA9,CA12, and to establish a correlation with clinicopathological features. Si RNA interference plasmid was constructed with lentivirus vector to silence HIF-2 偽, and MCF-7 cells were cultured and transfected with JNK inhibitor SP600125. MCF-7 cells and HIF-2 偽 silencing cells HIF-2 偽, 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 偽 in T2 and 鈪，
本文編號(hào)：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 偽 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 偽 and CA9,CA12, and to establish a correlation with clinicopathological features. Si RNA interference plasmid was constructed with lentivirus vector to silence HIF-2 偽, and MCF-7 cells were cultured and transfected with JNK inhibitor SP600125. MCF-7 cells and HIF-2 偽 silencing cells HIF-2 偽, 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 偽 in T2 and 鈪，
本文編號(hào)：2395168
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