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APRIL與宮頸癌的相關性研究

發(fā)布時間:2018-07-31 08:50
【摘要】:研究背景: APRIL(a proliferation-inducing ligand,增殖誘導配體)是腫瘤壞死因子(TNF)超家族的成員之一。有膜結(jié)合型、可溶型兩種活性形式。二者均可以促進腫瘤細胞系的增殖。APRIL在正常組織中的表達量很低,但在腫瘤細胞株和腫瘤組織中如結(jié)直腸癌、肺癌、血液系統(tǒng)腫瘤、乳腺癌、黑色素瘤、膀胱癌等組織中均有高水平表達。早期臨床研究發(fā)現(xiàn),APRIL在宮頸鱗癌組織中的表達,無論在m RNA還是在蛋白水平均顯著高于正常宮頸組織及鱗狀上皮內(nèi)病變組織,并且隨著細胞增殖與異型性的加重,表達水平逐漸增高。但是,在目前尚無對于APRIL與宮頸癌的分期、分級、病理分型及淋巴結(jié)轉(zhuǎn)移之間關聯(lián)的報道,也未見有APRIL在癌組織中的表達與宮頸癌預后之間關聯(lián)的報道。 本課題我們將研究APRIL與宮頸癌之間的關系,對正常宮頸組織或慢性宮頸炎組織、宮頸癌前病變組織、宮頸癌組織中的不同病理分型、分期、分級、淋巴結(jié)轉(zhuǎn)移中APRIL蛋白表達情況進行研究,應用免疫組化法檢測APRIL蛋白的表達情況,研究APRIL的表達與宮頸癌之間的關系,分析APRIL與宮頸癌的病理分型,分期,分級及淋巴結(jié)轉(zhuǎn)移的關聯(lián)。并應用生存分析方法回顧性分析行手術治療的宮頸癌患者的臨床病理資料,分析APRIL在宮頸癌組織中的表達與宮頸癌預后之間的關聯(lián),,同時對可能影響宮頸癌預后的多個因素進行單因素及多因素統(tǒng)計分析,用于指導術后輔助治療。 臨床研究發(fā)現(xiàn),APRIL在宮頸鱗癌組織中的表達,隨著細胞增殖與異型性的加重表達水平逐漸增高。根據(jù)以上研究結(jié)果,我們設想,APRIL蛋白的表達隨宮頸癌的分型、分期、分級及淋巴結(jié)的轉(zhuǎn)移增加而增加。為了驗證以上設想,我們對77例宮頸癌患者病理切片中的APRIL蛋白進行檢測,同時與30例正;蚵詫m頸炎組織及45例宮頸癌前病變組織進行比較,分析APRIL蛋白表達情況。再分析APRIL蛋白在癌組織中的表達與宮頸癌預后之間的關聯(lián)。 第一部分各宮頸組織中APRIL蛋白的表達及其與宮頸癌的關系研究目的: 研究各宮頸組織中APRIL蛋白的表達及其與宮頸癌分型、分期、分級、淋巴結(jié)轉(zhuǎn)移之間的關系。研究方法: 采用免疫組化法檢測77例宮頸癌組織,30例正常或慢性宮頸炎組織及45例宮頸癌前病變組織中的APRIL蛋白表達水平。研究結(jié)果:1.正常或慢性宮頸炎組織,宮頸癌前病變組織,宮頸癌組織中APRIL蛋白表達比較,差異有統(tǒng)計學意義(p0.05);2.不同分化的宮頸癌組織中的APRIL蛋白表達比較,差異有統(tǒng)計學意義(p0.05);3.宮頸鱗癌,腺鱗癌,腺癌組織中APRIL蛋白表達比較,差異無統(tǒng)計學意義(p0.05);4.不同分期的宮頸癌組織中APRIL蛋白表達比較,差異無統(tǒng)計學意義(p0.05);5.宮頸癌患者有盆腔淋巴結(jié)轉(zhuǎn)移者與無盆腔淋巴結(jié)轉(zhuǎn)移者宮頸癌組織中的APRIL蛋白表達比較,差異無統(tǒng)計學意義(p0.05)。結(jié)論: APRIL蛋白在正;蚵詫m頸炎組織,宮頸癌前病變組織,宮頸癌組織中的表達呈遞增趨勢;APRIL蛋白的表達隨宮頸癌的組織分化程度降低而增高,但其表達與宮頸癌的分期、臨床病理分型及盆腔淋巴結(jié)轉(zhuǎn)移無關。 第二部分宮頸癌組織中APRIL蛋白的表達與宮頸癌患者預后 的關聯(lián)研究目的: 分析APRIL蛋白在癌組織中的表達與宮頸癌患者預后之間的關聯(lián),同時分析影響手術治療宮頸癌患者預后的多個因素,用于指導術后輔助治療。研究方法: 回顧性分析第一部分中行手術治療的59例IB期及IIA期宮頸癌患者的臨床病理資料,對7個非重復特征性因素進行單因素及多因素統(tǒng)計分析。研究結(jié)果: 59例患者5年生存率為81.4%,其中APRIL蛋白(-)為85.7%,APRIL蛋白(+)為80.8%;IB期為83.3%,IIA期為72.7%。APRIL蛋白(-)與APRIL蛋白(+)組的總體生存曲線差異無統(tǒng)計學意義(P0.05)。單因素生存分析得出與宮頸癌患者預后有關的因素有:臨床病理分型、組織學分化、淋巴結(jié)轉(zhuǎn)移(P0.05)。多因素生存分析顯示臨床病理分型、組織學分化及淋巴結(jié)轉(zhuǎn)移是影響宮頸癌患者預后的危險因素(P0.05)。結(jié)論: 宮頸癌組織中APRIL蛋白的表達情況與預后無關;臨床病理分型、組織分化程度以及淋巴結(jié)轉(zhuǎn)移是影響早期宮頸癌患者預后的有關因素,早期宮頸癌患者可根據(jù)此影響預后因素指導術后輔助治療。
[Abstract]:Research background:
APRIL (a proliferation-inducing ligand, proliferation inducing ligand) is one of the members of the tumor necrosis factor (TNF) superfamily. There are two forms of membrane binding and soluble type. The two can promote the proliferation of tumor cell lines with low expression in normal tissues, but in tumor cell lines and tumor tissues, such as colorectal cancer, lung Early clinical studies have found that the expression of APRIL in the squamous cell carcinoma of the cervix is significantly higher in M RNA or in protein levels than in normal cervical tissues and squamous epithelium, and with the increase of cell proliferation and heteromorphology, However, there are no reports of the association between the stages, classification, pathological classification and lymph node metastasis of APRIL and cervical cancer, and there are no reports of the association between the expression of APRIL in the cancer tissues and the prognosis of cervical cancer.
We will study the relationship between APRIL and cervical cancer, and study the expression of APRIL protein in the normal cervical tissue or chronic cervicitis, cervical precancerous tissue, cervical cancer tissues, different pathological types, stages, classification and lymph node metastasis. The expression of APRIL protein should be detected by immunohistochemical method, and APR should be studied. The relationship between the expression of IL and cervical cancer, the correlation between the pathological classification, staging, classification and lymph node metastasis of APRIL and cervical cancer, and a retrospective analysis of the clinicopathological data of the patients with cervical cancer treated by the survival analysis, and the correlation between the expression of APRIL in cervical cancer and the prognosis of cervical cancer. Univariate and multivariate statistical analyses were conducted on multiple factors that might affect the prognosis of cervical cancer, and were used to guide postoperative adjuvant therapy.
Clinical studies have found that the expression of APRIL in the squamous cell carcinoma of the cervix is increasing with the increasing expression of cell proliferation and heterotypic expression. According to the above findings, we envisage that the expression of APRIL protein increases with the classification, staging, classification and lymph node metastasis of cervical cancer. In order to verify the above assumption, we have 77 cases of cervix. The APRIL protein in the pathological sections of the cancer patients was detected and compared with 30 normal or chronic cervicitis and 45 cases of cervical precancerous lesions, and the expression of APRIL protein was analyzed. The relationship between the expression of APRIL protein in the cancer tissue and the prognosis of cervical cancer was analyzed.
Part one: the expression of APRIL protein in cervical tissues and its relationship with cervical cancer.
To study the expression of APRIL protein in cervical tissues and its relationship with the classification, staging, grading and lymph node metastasis of cervical cancer.
The expression of APRIL protein in 77 cases of cervical cancer, 30 cases of normal or chronic cervicitis and 45 cases of cervical precancerous lesions were detected by immunohistochemistry. Results: 1. normal or chronic cervicitis tissues, cervical precancerous lesions, and APRIL protein expression in cervical cancer tissues were statistically significant (P0.05); 2. There was significant difference in the expression of APRIL protein in the differentiated cervical cancer tissues (P0.05), and there was no significant difference in the expression of APRIL protein in 3. cervical squamous cell carcinoma, adenocarcinoma and adenocarcinoma tissue (P0.05), and there was no statistical difference between the APRIL protein table in 4. different stages of cervical cancer (P0.05); 5. cervical cancer patients. There was no significant difference in the expression of APRIL protein between patients with pelvic lymph node metastasis and those without pelvic lymph node metastasis (p0.05).
The expression of APRIL protein increased in normal or chronic cervicitis, precancerous tissue and cervical cancer tissue, and the expression of APRIL protein increased with the degree of tissue differentiation of cervical cancer, but its expression was not related to the stage of cervical cancer, clinicopathological classification and pelvic lymph node metastasis.
The second part is the expression of APRIL protein in cervical cancer and the prognosis of cervical cancer patients.
The purpose of the association study:
To analyze the association between the expression of APRIL protein in the cancer tissue and the prognosis of cervical cancer patients, and to analyze the factors affecting the prognosis of the patients with cervical cancer and to guide postoperative adjuvant therapy.
A retrospective analysis of the clinicopathological data of 59 patients with stage IB and IIA cervical cancer in the first part of the first part of the operation. A single factor and multiple factor analysis were performed on 7 non repetitive characteristic factors. The results were as follows:
The 5 year survival rate of 59 patients was 81.4%, of which APRIL protein (-) was 85.7%, APRIL protein (+) was 80.8%, IB phase was 83.3%, and the overall survival curve of 72.7%.APRIL protein (-) and APRIL protein (+) group was not statistically significant (P0.05). The factors associated with the prognosis of cervical cancer patients with single factor survival analysis were clinical pathology. Classification, histological differentiation, lymph node metastasis (P0.05). Multivariate survival analysis showed that the clinicopathological classification, histological differentiation and lymph node metastasis were risk factors for the prognosis of cervical cancer patients (P0.05).
The expression of APRIL protein in cervical cancer is not related to the prognosis. Clinicopathological classification, degree of tissue differentiation and lymph node metastasis are related factors affecting the prognosis of early cervical cancer patients. Early cervical cancer patients can guide postoperative adjuvant therapy according to the influence of prognostic factors.
【學位授予單位】:廣西醫(yī)科大學
【學位級別】:碩士
【學位授予年份】:2014
【分類號】:R737.33

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