农村和城市食管鳞癌患者生存对比分析及P53在两组患者中的表达和临床意义

发布时间：2018-03-09 04:35

  本文选题：食管鳞癌　切入点：农村和城市　出处：《郑州大学》2017年硕士论文　论文类型：学位论文

【摘要】：1 研究背景和目的中国人食管癌具有典型的地域性分布特征,具有显著的高低发区之分,高、低发区的发病率和死亡率可相差高达500倍[1],而高发区主要位于山区和农村,城市地区相对少见。中国人食管癌97%以上的组织学类型是食管鳞状细胞癌(简称食管鳞癌),与西方国家以食管腺癌为主要组织学类型明显不同。食管癌的发生发展是多因素、多基因共同作用下的多阶段演进的病理变化过程。营养元素缺乏,特别是维生素和微量元素的缺乏是中国人食管癌发生的主要危险因素之一[2]。因此,食管癌在我国被称为是一种“穷病”。亚硝胺暴露、霉菌毒素感染和人类乳头瘤病毒(human papilloma virus,HPV)感染也被认为是中国食管癌高发区居民食管癌发生的重要危险因素[3]。因此我国食管癌高发区食管鳞癌患者,特别是农村患者,暴露于环境中危险因素的程度可能更高。与此相反,城市食管癌患者在亚硝胺暴露、生物危险因素感染程度方面可能更低。同时,城市患者在饮食结构、营养状况、经济水平及医疗资源方面显著优于农村患者。这些可能是城市地区食管癌患者少见的原因之一,并可能会对预后产生一定的影响。但是有关农村和城市食管鳞癌患者生存对比分析的报道非常少见。现有的P53基因突变谱分析结果表明,黄曲霉毒素B可引起p53基因249号密码子第三位的碱基颠换,从而形成其特殊的突变;环境中的亚硝胺也可引起P53的点突变[4-5]。Wang等[6]报道了P53-Rb信号转导通路的改变是食管癌发生过程中的重要分子机制。农村和城市食管鳞癌患者在发病危险因素的暴露程度方面有很大的差异,然而有关P53分别在农村和城市食管鳞癌患者组织中的表达是否有差异,及其分别与临床病理特征的关系研究尚为少见。因此,本研究通过对来自农村和城市的41,520例均行食管癌根治术的食管鳞癌患者进行对比分析,探讨农村和城市患者的生存差异及其影响因素和P53分别在两组患者中的表达及其临床意义,对食管癌防控、高危人群预警和相关分子检测提供可行性的决策依据。2 材料与方法2.1 研究对象本研究41,520例食管鳞癌患者的一般资料、病理信息、临床诊疗和随访结果均来自郑州大学第一附属医院河南省食管癌重点开放实验室50万例食管癌及贲门癌临床信息及生物样本大数据库(1973-2015年)。农村患者37,968例,占91.4%,其中男性23,685例,平均诊断年龄58.89±8.64岁;女性14,283例,平均诊断年龄59.51±8.49岁。城市患者3,552例,其中男性2,400例,平均诊断年龄60.65±9.10岁;女性1,152例,平均诊断年龄62.31±9.13岁。所有患者均行食管癌根治术治疗。2.2 临床信息收集与随访患者的一般信息及病理信息等均来自患者所在治疗医院的住院病历记录,包括一般信息、详细地址、联系方式等,术后病理诊断均明确,并到相关治疗医院进行患者临床及病理信息的核查和补充。通过电话随访、入户调查、村医询问等方式进行患者的生存随访,末次随访时间为2016年4月,随访成功率为92%。2.3 方法1.分别对来农村的37,968例和城市的3,552例食管鳞癌患者临床资料进行回顾性分析,主要包括患者的一般信息(性别、年龄、高低发区)和病理信息(大体类型、分化程度、淋巴结是否转移、残端癌的有无和TNM分期。2.分别随机选取56例农村患者食管癌组织和距癌组织肿块5cm以上的正常组织,以及29例城市患者食管癌组织和距癌组织肿块5cm以上的正常组织进行免疫组化实验,检测P53蛋白的表达情况,并分析食管癌组织中P53表达与各组患者临床特征的关系,并进一步分析癌组织中P53蛋白的表达对两组患者预后的影响。3.采用SPSS 21.0软件分析系统,农村和城市食管鳞癌患者的一般信息(性别、年龄)和病理信息(如肿瘤部位、大体类型)采用卡方检验;生存时间按年计算,采用寿命表法计算1、3、5、年生存率,Kaplan-Meier和Log-rank法分析生存差异;采用多因素Cox比例风险回归模型分析生存主要影响因素,检验水准为α=0.05。3结果3.1农村和城市食管鳞癌患者性别、年龄、高低发区和病理特征等分布41,520例食管鳞癌患者中,农村患者37,968例,占91.4%,远高于城市患者(3,552例,8.6%)。农村和城市食管鳞癌患者的男女比例分别为1.7:1和2.1:1,性别分布存在明显差异(χ2=37.405,P=0.000)。农村男性(58.89±8.64岁)和女性(59.51±8.49岁)食管癌患者平均诊断年龄均明显低于城市患者(男,60.65±9.10岁;女,62.31±9.13岁)(P=0.000)。农村食管癌患者高发区所占比例高于城市(农村高发区患者:65.0%vs.城市高发区患者:46.7%,χ2=467.639,P=0.000);农村患者早期癌(0+Ⅰ期)所占比例(11.8%)明显低于城市(13.9%),而农村中晚期(Ⅱ+Ⅲ+Ⅳ期)患者所占比例(88.2%)高于城市(86.1%)(χ2=25.787,P=0.000)。3.2 农村和城市食管鳞癌患者生存对比及影响因素分析寿命表法分析结果显示:农村和城市食管鳞癌患者的1、3、5年生存率分别为90.0%、69.0%、55.0%和87.0%、64.0%、52.0%。Kaplan-Meier和Log-rank总体分析显示:农村食管癌患者整体生存明显优于城市患者(χ2=15.503,P=0.000)。年龄、性别和病理分期多因素分层分析显示:农村≥50岁男性和≥50岁女性中期(Ⅱa、Ⅱb期)的患者生存明显优于城市患者(男:χ2=14.868,P=0.000;女:χ2=8.025,P=0.005);但是,农村和城市患者在早期(0、Ⅰ期)和晚期(Ⅲ、Ⅳ期)生存无差异(P0.05)。3.3 多因素Cox比例风险回归模型分析Cox比例风险回归模型分析显示:影响农村食管鳞癌患者生存的独立危险因素为性别、年龄、高低发区、TNM分期、肿瘤分化程度、肿瘤部位;而影响城市食管鳞癌患者生存的独立危险因素为性别、年龄、高低发区、TNM分期;农村和城市患者综合分析显示:男性、诊断年龄≥50岁、城市、低发区、TNM分期加深、肿瘤分化差、上段肿瘤、残端癌阳性是食管鳞癌患者预后差的独立危险因素,而女性、年龄50岁、农村、高发区、肿瘤分化较好、残端癌阴性是食管鳞癌患者预后好的保护因素。3.4 P53分别在农村和城市食管鳞癌患者中的表达及对预后的分析农村食管鳞癌患者食管正常组织和食管癌组织P53的阳性表达率分别为7.1%(4/56)和64.3%(36/56),两者间P53的表达具有显著的差异(P0.05);城市食管鳞癌患者食管正常组织和食管癌组织P53的阳性表达率分别为6.9%(2/29)和61.1%(18/29),两者间P53的表达也具有显著的差异(P0.05);但是农村和城市间患者食管癌组织P53的阳性表达率相似(农村:64.3%vs城市:62.1%,P0.05)。农村和城市患者癌组织中P53的表达均与性别、年龄、分化程度和淋巴结是否转移无关(P0.05)。农村患者食管癌组织中P53表达阴性与表达阳性生存相似(χ2=0.163,P=0.686),与农村患者相似,城市患者食管癌组织中P53表达阴性与表达阳性生存也相似(χ2=0.267,P=0.605)。食管癌组织中P53的阳性表达均不是影响农村、城市患者生存的独立危险因素,也不是影响农村城市整体食管鳞癌患者生存的独立危险因素。4 结论1)农村地区食管癌患者整体生存优于城市患者;2)男性、诊断年龄≥50岁、城市、低发区、TNM分期程度加深、肿瘤分化差、上段肿瘤、残端癌阳性是食管鳞癌患者预后差的独立危险因素;3)P53在食管癌组织中的阳性表达率远高于食管正常组织,可作为食管癌检测的一个分子指标;但P53分别在农村和城市食管鳞癌患者食管癌组织中的阳性表达率相似,P53在食管癌组织中的阳性表达不是影响食管鳞癌患者生存的独立危险因素,传统的病理信息仍是判断食管癌患者预后的重要参考指标。
[Abstract]:1 background and objective Chinese esophageal cancer has the typical characteristics of regional distribution, has a significant level of development zones, high and low incidence areas of morbidity and mortality is 500 times as high as [1], while the high incidence area mainly located in mountainous and rural areas, the city is relatively rare. More than 97% Chinese human esophageal cancer the histological type is esophageal squamous cell carcinoma (ESCC), and the western countries to esophageal adenocarcinoma was the main histological types were significantly different. The development of esophageal carcinoma is a multi factor, multi-stage process of pathological changes of multiple genes. The evolution of nutrient deficiency, especially the lack of vitamins and trace elements the main risk of human esophageal cancer China occurred in one of the factors of [2]. therefore, esophageal cancer in China is said to be a "poor" disease. Nitrosamine exposure, mycotoxins and infection of human papilloma virus (human papilloma VI Rus, HPV) [3]. infection is also considered an important risk factor for esophageal cancer China residents in high incidence area of esophageal cancer occurred in our country so high incidence areas of esophageal cancer patients with squamous cell carcinoma of the esophagus, especially rural patients, exposure to environmental risk factors may be more high. On the contrary, the City food tube cancer patients exposed to nitrite amine, biological risk factors for infection degree may be lower. At the same time, the nutritional status of patients in the city, the diet structure, economic level and medical resources significantly better than rural patients. These may be the city area rare in patients with esophageal carcinoma is one of the reasons, and may have some impact on the prognosis. But the analysis of the rural and city of esophagus the survival of patients with squamous cell carcinoma of comparative reports are very rare. The P53 gene mutation spectrum analysis showed that aflatoxin B can cause p53 gene codon 249 base third bit for Britain, which Form the special mutation; nitrosamines in the environment can also be caused by point mutation of P53 [4-5].Wang [6] reported that the P53-Rb signal transduction pathway changes is an important molecular mechanism of the occurrence of esophageal cancer. The rural and city of patients with esophageal squamous cell carcinoma have great differences in the risk factors of the exposure side, however, about P53 the expression in the countryside and city respectively in patients with esophageal squamous cell carcinoma tissues is whether there are differences, and the relationship with clinical pathological features is still rare. Therefore, this research through the comparative analysis of 41520 cases from rural and city underwent esophageal cancer radical surgery in patients with esophageal squamous cell carcinoma, and to explore the factors and survival of rural P53 the difference with city and influence respectively in the two groups, the expression and clinical significance of esophageal cancer prevention, early warning and detection of high-risk decision related molecules provide feasible General information, on the basis of.2 materials and methods 2.1 subjects in this study of 41520 cases of patients with esophageal squamous cell carcinoma pathological information, clinical diagnosis and treatment and follow-up results were from the First Affiliated Hospital of Zhengzhou University Henan Province Key Laboratory of esophageal cancer in 500 thousand cases of esophageal cancer and cardia cancer clinical information and biological sample database (1973-2015 years). Patients in rural areas in 37968 cases. 91.4%, there were 23685 males, the average age at diagnosis was 58.89 + 8.64 years; 14283 were female, the average age at diagnosis was 59.51 + 8.49 years. 3552 cases of patients in city, there were 2400 males, the average age at diagnosis was 60.65 + 9.10 years; 1152 were female, the average age at diagnosis was 62.31 + 9.13 years. All patients underwent esophageal cancer radical operation in the treatment of.2.2 clinical information collection and follow-up of patients with general information and pathological information were from patients where the treatment of hospital medical records, including general information, detailed Address, contact, postoperative pathological diagnosis were clear, and to the hospital for treatment of patients with clinical and pathological information verification and supplement. Through telephone follow-up survey, the village doctors ask way of survival patients, the last follow-up time is April 2016, follow-up success rate of 92%.2.3 1. respectively 37968 to the city of rural patients and 3552 cases of esophageal squamous cell carcinoma were retrospectively analyzed, including general information of patients (gender, age, level of area) and pathological information (gross type, differentiation degree, lymph node metastasis, stump cancer and the TNM staging.2. were randomly selected 56 cases were esophageal cancer and cancer tissue mass of more than 5cm from the normal tissue, and 29 cases of patients with esophageal cancer and the city from the cancer tissue of normal tissue masses above 5cm immunohistochemical experiments, detection of P53 eggs The expression of white, and analyze the relationship between P53 expression and clinical features of patients with esophageal cancer tissues, and further analysis of the expression of P53 protein in cancer tissue of two groups of patients influence the prognosis of.3. was analyzed by SPSS 21 software system, rural city and general information of patients with esophageal squamous cell carcinoma (the gender, age and pathology (information) as the tumor site, gross type) by chi square test; survival time was calculated by 1,3,5, calculated the life table method, survival rate, survival analysis between Kaplan-Meier and Log-rank; using multivariate Cox proportional hazard regression model in survival analysis of the main factors, inspection standards for a =0.05.3 city and countryside results in 3.1 patients with esophageal squamous cell carcinoma gender, age, level of area distribution and pathological features of 41520 cases of esophageal squamous cell carcinoma, 37968 cases of patients in rural areas, accounting for 91.4%, far higher than the city of patients (3552 cases, 8.6%) in rural areas and the city. Esophageal squamous cell carcinoma in patients with male to female ratio were 1.7:1 and 2.1:1, there are obvious differences in gender distribution (2=37.405, P=0.000). The rural male (58.89 + 8.64) and women (59.51 + 8.49) in patients with esophageal cancer were significantly lower than the city average diagnostic age patients (male, 60.65 + 9.10 years; female, 62.31. At the age of 9.13) (P=0.000). The high incidence areas of esophageal carcinoma patients higher than the proportion of the city (rural high incidence area of patients: 65.0%vs. city high incidence area of patients: 46.7%, X 2=467.639, P=0.000); early cancer (0+ stage) in rural areas the proportion (11.8%) was significantly lower than that of the city (13.9%), while the rural advanced (II + III + IV) proportion of patients (88.2%) was higher than that of the city (86.1%) (2=25.787, P=0.000) life table analysis showed.3.2 factors of rural and city survival of patients with esophageal squamous cell carcinoma: comparison and Analysis on 1,3,5 year survival rate of rural and city in patients with esophageal squamous cell carcinoma were 90% ,69.0%,55.0%鍜，

本文编号：1587043