發(fā)布時(shí)間：2018-03-09 04:35

  本文選題：食管鱗癌　切入點(diǎn)：農(nóng)村和城市　出處：《鄭州大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：1 研究背景和目的中國人食管癌具有典型的地域性分布特征,具有顯著的高低發(fā)區(qū)之分,高、低發(fā)區(qū)的發(fā)病率和死亡率可相差高達(dá)500倍[1],而高發(fā)區(qū)主要位于山區(qū)和農(nóng)村,城市地區(qū)相對(duì)少見。中國人食管癌97%以上的組織學(xué)類型是食管鱗狀細(xì)胞癌(簡稱食管鱗癌),與西方國家以食管腺癌為主要組織學(xué)類型明顯不同。食管癌的發(fā)生發(fā)展是多因素、多基因共同作用下的多階段演進(jìn)的病理變化過程。營養(yǎng)元素缺乏,特別是維生素和微量元素的缺乏是中國人食管癌發(fā)生的主要危險(xiǎn)因素之一[2]。因此,食管癌在我國被稱為是一種“窮病”。亞硝胺暴露、霉菌毒素感染和人類乳頭瘤病毒(human papilloma virus,HPV)感染也被認(rèn)為是中國食管癌高發(fā)區(qū)居民食管癌發(fā)生的重要危險(xiǎn)因素[3]。因此我國食管癌高發(fā)區(qū)食管鱗癌患者,特別是農(nóng)村患者,暴露于環(huán)境中危險(xiǎn)因素的程度可能更高。與此相反,城市食管癌患者在亞硝胺暴露、生物危險(xiǎn)因素感染程度方面可能更低。同時(shí),城市患者在飲食結(jié)構(gòu)、營養(yǎng)狀況、經(jīng)濟(jì)水平及醫(yī)療資源方面顯著優(yōu)于農(nóng)村患者。這些可能是城市地區(qū)食管癌患者少見的原因之一,并可能會(huì)對(duì)預(yù)后產(chǎn)生一定的影響。但是有關(guān)農(nóng)村和城市食管鱗癌患者生存對(duì)比分析的報(bào)道非常少見�，F(xiàn)有的P53基因突變譜分析結(jié)果表明,黃曲霉毒素B可引起p53基因249號(hào)密碼子第三位的堿基顛換,從而形成其特殊的突變;環(huán)境中的亞硝胺也可引起P53的點(diǎn)突變[4-5]。Wang等[6]報(bào)道了P53-Rb信號(hào)轉(zhuǎn)導(dǎo)通路的改變是食管癌發(fā)生過程中的重要分子機(jī)制。農(nóng)村和城市食管鱗癌患者在發(fā)病危險(xiǎn)因素的暴露程度方面有很大的差異,然而有關(guān)P53分別在農(nóng)村和城市食管鱗癌患者組織中的表達(dá)是否有差異,及其分別與臨床病理特征的關(guān)系研究尚為少見。因此,本研究通過對(duì)來自農(nóng)村和城市的41,520例均行食管癌根治術(shù)的食管鱗癌患者進(jìn)行對(duì)比分析,探討農(nóng)村和城市患者的生存差異及其影響因素和P53分別在兩組患者中的表達(dá)及其臨床意義,對(duì)食管癌防控、高危人群預(yù)警和相關(guān)分子檢測(cè)提供可行性的決策依據(jù)。2 材料與方法2.1 研究對(duì)象本研究41,520例食管鱗癌患者的一般資料、病理信息、臨床診療和隨訪結(jié)果均來自鄭州大學(xué)第一附屬醫(yī)院河南省食管癌重點(diǎn)開放實(shí)驗(yàn)室50萬例食管癌及賁門癌臨床信息及生物樣本大數(shù)據(jù)庫(1973-2015年)。農(nóng)村患者37,968例,占91.4%,其中男性23,685例,平均診斷年齡58.89±8.64歲;女性14,283例,平均診斷年齡59.51±8.49歲。城市患者3,552例,其中男性2,400例,平均診斷年齡60.65±9.10歲;女性1,152例,平均診斷年齡62.31±9.13歲。所有患者均行食管癌根治術(shù)治療。2.2 臨床信息收集與隨訪患者的一般信息及病理信息等均來自患者所在治療醫(yī)院的住院病歷記錄,包括一般信息、詳細(xì)地址、聯(lián)系方式等,術(shù)后病理診斷均明確,并到相關(guān)治療醫(yī)院進(jìn)行患者臨床及病理信息的核查和補(bǔ)充。通過電話隨訪、入戶調(diào)查、村醫(yī)詢問等方式進(jìn)行患者的生存隨訪,末次隨訪時(shí)間為2016年4月,隨訪成功率為92%。2.3 方法1.分別對(duì)來農(nóng)村的37,968例和城市的3,552例食管鱗癌患者臨床資料進(jìn)行回顧性分析,主要包括患者的一般信息(性別、年齡、高低發(fā)區(qū))和病理信息(大體類型、分化程度、淋巴結(jié)是否轉(zhuǎn)移、殘端癌的有無和TNM分期。2.分別隨機(jī)選取56例農(nóng)村患者食管癌組織和距癌組織腫塊5cm以上的正常組織,以及29例城市患者食管癌組織和距癌組織腫塊5cm以上的正常組織進(jìn)行免疫組化實(shí)驗(yàn),檢測(cè)P53蛋白的表達(dá)情況,并分析食管癌組織中P53表達(dá)與各組患者臨床特征的關(guān)系,并進(jìn)一步分析癌組織中P53蛋白的表達(dá)對(duì)兩組患者預(yù)后的影響。3.采用SPSS 21.0軟件分析系統(tǒng),農(nóng)村和城市食管鱗癌患者的一般信息(性別、年齡)和病理信息(如腫瘤部位、大體類型)采用卡方檢驗(yàn);生存時(shí)間按年計(jì)算,采用壽命表法計(jì)算1、3、5、年生存率,Kaplan-Meier和Log-rank法分析生存差異;采用多因素Cox比例風(fēng)險(xiǎn)回歸模型分析生存主要影響因素,檢驗(yàn)水準(zhǔn)為α=0.05。3結(jié)果3.1農(nóng)村和城市食管鱗癌患者性別、年齡、高低發(fā)區(qū)和病理特征等分布41,520例食管鱗癌患者中,農(nóng)村患者37,968例,占91.4%,遠(yuǎn)高于城市患者(3,552例,8.6%)。農(nóng)村和城市食管鱗癌患者的男女比例分別為1.7:1和2.1:1,性別分布存在明顯差異(χ2=37.405,P=0.000)。農(nóng)村男性(58.89±8.64歲)和女性(59.51±8.49歲)食管癌患者平均診斷年齡均明顯低于城市患者(男,60.65±9.10歲;女,62.31±9.13歲)(P=0.000)。農(nóng)村食管癌患者高發(fā)區(qū)所占比例高于城市(農(nóng)村高發(fā)區(qū)患者:65.0%vs.城市高發(fā)區(qū)患者:46.7%,χ2=467.639,P=0.000);農(nóng)村患者早期癌(0+Ⅰ期)所占比例(11.8%)明顯低于城市(13.9%),而農(nóng)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 農(nóng)村和城市食管鱗癌患者生存對(duì)比及影響因素分析壽命表法分析結(jié)果顯示:農(nóng)村和城市食管鱗癌患者的1、3、5年生存率分別為90.0%、69.0%、55.0%和87.0%、64.0%、52.0%。Kaplan-Meier和Log-rank總體分析顯示:農(nóng)村食管癌患者整體生存明顯優(yōu)于城市患者(χ2=15.503,P=0.000)。年齡、性別和病理分期多因素分層分析顯示:農(nóng)村≥50歲男性和≥50歲女性中期(Ⅱa、Ⅱb期)的患者生存明顯優(yōu)于城市患者(男:χ2=14.868,P=0.000;女:χ2=8.025,P=0.005);但是,農(nóng)村和城市患者在早期(0、Ⅰ期)和晚期(Ⅲ、Ⅳ期)生存無差異(P0.05)。3.3 多因素Cox比例風(fēng)險(xiǎn)回歸模型分析Cox比例風(fēng)險(xiǎn)回歸模型分析顯示:影響農(nóng)村食管鱗癌患者生存的獨(dú)立危險(xiǎn)因素為性別、年齡、高低發(fā)區(qū)、TNM分期、腫瘤分化程度、腫瘤部位;而影響城市食管鱗癌患者生存的獨(dú)立危險(xiǎn)因素為性別、年齡、高低發(fā)區(qū)、TNM分期;農(nóng)村和城市患者綜合分析顯示:男性、診斷年齡≥50歲、城市、低發(fā)區(qū)、TNM分期加深、腫瘤分化差、上段腫瘤、殘端癌陽性是食管鱗癌患者預(yù)后差的獨(dú)立危險(xiǎn)因素,而女性、年齡50歲、農(nóng)村、高發(fā)區(qū)、腫瘤分化較好、殘端癌陰性是食管鱗癌患者預(yù)后好的保護(hù)因素。3.4 P53分別在農(nóng)村和城市食管鱗癌患者中的表達(dá)及對(duì)預(yù)后的分析農(nóng)村食管鱗癌患者食管正常組織和食管癌組織P53的陽性表達(dá)率分別為7.1%(4/56)和64.3%(36/56),兩者間P53的表達(dá)具有顯著的差異(P0.05);城市食管鱗癌患者食管正常組織和食管癌組織P53的陽性表達(dá)率分別為6.9%(2/29)和61.1%(18/29),兩者間P53的表達(dá)也具有顯著的差異(P0.05);但是農(nóng)村和城市間患者食管癌組織P53的陽性表達(dá)率相似(農(nóng)村:64.3%vs城市:62.1%,P0.05)。農(nóng)村和城市患者癌組織中P53的表達(dá)均與性別、年齡、分化程度和淋巴結(jié)是否轉(zhuǎn)移無關(guān)(P0.05)。農(nóng)村患者食管癌組織中P53表達(dá)陰性與表達(dá)陽性生存相似(χ2=0.163,P=0.686),與農(nóng)村患者相似,城市患者食管癌組織中P53表達(dá)陰性與表達(dá)陽性生存也相似(χ2=0.267,P=0.605)。食管癌組織中P53的陽性表達(dá)均不是影響農(nóng)村、城市患者生存的獨(dú)立危險(xiǎn)因素,也不是影響農(nóng)村城市整體食管鱗癌患者生存的獨(dú)立危險(xiǎn)因素。4 結(jié)論1)農(nóng)村地區(qū)食管癌患者整體生存優(yōu)于城市患者;2)男性、診斷年齡≥50歲、城市、低發(fā)區(qū)、TNM分期程度加深、腫瘤分化差、上段腫瘤、殘端癌陽性是食管鱗癌患者預(yù)后差的獨(dú)立危險(xiǎn)因素;3)P53在食管癌組織中的陽性表達(dá)率遠(yuǎn)高于食管正常組織,可作為食管癌檢測(cè)的一個(gè)分子指標(biāo);但P53分別在農(nóng)村和城市食管鱗癌患者食管癌組織中的陽性表達(dá)率相似,P53在食管癌組織中的陽性表達(dá)不是影響食管鱗癌患者生存的獨(dú)立危險(xiǎn)因素,傳統(tǒng)的病理信息仍是判斷食管癌患者預(yù)后的重要參考指標(biāo)。
[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，

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