宫颈癌中CLIC4、TGF-β1和α-SMA的表达及意义

发布时间：2018-04-02 01:20

  本文选题：宫颈癌　切入点：宫颈上皮内瘤变　出处：《郑州大学》2017年硕士论文

【摘要】：背景及目的宫颈癌是造成女性死亡的最常见的妇科恶性肿瘤之一。中国每年新发病例及死亡人数在全球居高不下,且发病率渐呈年轻化趋势,其浸润及转移是导致晚期宫颈癌患者死亡的重要原因。寻找宫颈癌在浸润和转移过程中的敏感指标或其发展中的关键因子,对提高宫颈癌患者生存率及生存质量非常重要。肿瘤的发生发展与肿瘤细胞所在微环境密切相关,结合文献及我们前期的研究结果显示,肿瘤相关成纤维细胞(tumor-associated fibroblasts,TAFs)为癌细胞周围基质的主要组成部分,在宫颈癌的恶性转化和进展中起着重要作用。成纤维细胞激活后表达a-SMA,成为肌纤维母细胞,即TAFs。a-SMA是成纤维细胞成为肿瘤基质的一个标志。TGF-β1是介导这种相互作用的关键细胞因子,但其发生发展的机制仍不清楚。已有研究显示,在乳腺癌、卵巢癌、结直肠癌等癌症中,TGF-β1可刺激癌周正常组织成纤维细胞的CLIC4水平升高,且CLIC4高表达于癌组织的肿瘤相关成纤维细胞。因此推测,CLIC4、TGF-β1和α-SMA在宫颈癌的发生发展中发挥作用,但目前国内外关于CLIC4在宫颈癌中的研究报道极少。我们采用免疫组织化学方法检测CLIC4、TGF-β1和α-SMA在117例宫颈癌、48例高级别鳞状上皮内瘤变(HSIL,即CINⅡ~Ⅱ)、28例慢性宫颈炎组织中的表达,并分析其表达与宫颈癌患者临床病理特征的关系以及三者表达的相关性,有助于研究宫颈癌细胞与TAFs之间相互作用原理,从而进一步揭示宫颈癌浸润转移的机制。材料和方法1.研究对象:收集郑州大学第一附属医院病理标本库2014年1月~2015年1月手术切除的宫颈癌患者的肿瘤组织117例(所有患者术前均未进行放化疗),HSIL患者的宫颈病变组织48例,另选取因非宫颈疾病切除子宫的患者的宫颈组织28例作为对照,2名有经验的病理组织学专家证实诊断。117例宫颈癌患者中:年龄29~70岁,中位年龄46岁;FIGO分期(2012年):I期67例,II期50例;组织学类型:鳞癌99例,腺癌18例;分化程度:G1 64例,G2 27例,G3 26例;间质浸润深度:≤间质1/2 82例,间质1/2 35例;淋巴结转移:有21例,无96例.2.实验方法:免疫组织化学SP法检测3组标本中CLIC4,TGF-β1和α-SMA的表达,分析其在3组之间的表达差异,探究其表达与临床病理因素的关系,并分析三者者之间表达的相关性。3.统计学分析:应用SPSS21.0统计软件进行统计处理。阳性率之间的比较应用χ~2检验,CLIC4,TGF-β1和α-SMA的表达相关性用Spearman等级相关分析。P0.05为差异有统计学意义。结果1.CLIC4在宫颈癌、CIN和慢性宫颈炎组织中的阳性表达率分别为76.92%、45.83%和10.71%。宫颈癌组织中CLIC4的表达率高于CIN和慢性宫颈炎,差异有统计学意义(P0.05)。宫颈癌组织中CLIC4的表达与淋巴结转移(χ2=4.84,P=0.04)和间质浸润深度(χ2=8.48,P=0.009)、FIGO分期(χ2=8.41,P=0.001)有关,与分化程度(χ2=2.50,P=0.12)、年龄(χ2=0.33,P=0.66)、组织学类型(χ2=1.08,P=0.37)无关。2.TGF-β1在宫颈癌组织中的阳性表达率为70.08%,在HSIL表达阳性率为47.91%,在慢性宫颈炎组织中为17.85%。宫颈癌组织中TGF-β1的表达率高于HSIL组织,差异有统计学意义(P0.05),宫颈癌组织中TGF-β1的表达率高于宫颈炎组织,差异有统计学意义(P0.05)。宫颈癌组织中TGF-β1的表达与淋巴结转移(χ2=5.08,P=0.03)和间质浸润深度(χ2=10.85,P=0.001)、FIGO分期(χ2=8.06,P=0.01)有关,与年龄(χ2=0.03,P=0.60)、分化程度(χ2=2.45,P=0.15)、组织学类型(χ2=0.60,P=0.58)无关。3.α-SMA宫颈癌组织中的阳性表达率为97.43%,在HSIL组织中表达阳性率为47.91%,在慢性宫颈炎中为7.14%。宫颈癌组织中α-SMA的表达率高于宫颈上皮内瘤变组织,差异有统计学意义(P0.05),宫颈癌组织中α-SMA的表达率高于宫颈炎组织,差异有统计学意义(P0.05)。宫颈癌组织中α-SMA的表达与淋巴结转移(χ2=14.08,P=0.001)和间质浸润深度(χ2=7.21,P=0.03)有关,与年龄(χ2=0.23,P=0.80)、FIGO分期(χ2=3.52,P=0.12)、组织学类型(χ2=0.76,P=0.40)、分化程度(χ2=2.30,P=0.26)无关。4.宫颈癌组织中CLIC4和TGF-β1的表达存在正相关(r=0.625,P=0.001);CLIC4和α-SMA的表达存在正相关(r=0.624,P=0.001)。结论1.宫颈癌组织中CLIC4、TGF-β1和α-SMA在宫颈癌组织中存在高表达,随着宫颈病变的进展,CLIC4、TGF-β1和α-SMA的表达率逐渐升高,提示CLIC4、TGF-β1和α-SMA与宫颈癌的发生发展有关。2.宫颈癌组织中CLIC4和TGF-β1的表达与宫颈癌淋巴结转移、间质浸润深度、FIGO分期有关;α-SMA的阳性表达与宫颈癌淋巴结转移、间质浸润深度有关。提示CLIC4、TGF-β1和α-SMA可能与宫颈癌的浸润和转移有关。
[Abstract]:Background and objective: cervical cancer is one of the causes of death in women the most common gynecological malignant tumor. China new cases every year and the death toll in the global high, and the incidence rate was gradually younger, its invasion and metastasis is the leading cause of death in patients with advanced cervical cancer. Cervical cancer to find key factors in the invasion and sensitive index in the process of the transfer or in its development, it is very important to improve the survival rate of patients with cervical cancer and quality of life. The occurrence and development of tumor and tumor cells are closely related to the microenvironment, combined with the literature and our previous studies showed that tumor associated fibroblasts (tumor-associated, fibroblasts, TAFs) as the main component of cancer cells around the matrix, which plays an important role in the malignant transformation and progression of cervical cancer. The expression of a-SMA in fibroblasts after activation into myofibroblasts, namely TAFs.a- SMA is the fibroblasts as a sign of.TGF- beta 1 tumor stromal cells are crucial factors mediating this interaction, but its development mechanism is still not clear. Studies have shown that in breast cancer, ovarian cancer, colorectal cancer and other cancers, TGF- beta 1 stimulates cancer Zhou Zheng tissue fibroblast cells with elevated levels of CLIC4, and the high expression of CLIC4 in cancer tissue of tumor associated fibroblasts. It was suggested that CLIC4, TGF- beta 1 and alpha -SMA in cervical cancer play an important role in the development at home and abroad, but the reports about CLIC4 in cervical cancer is less. We detected by immunohistochemical method CLIC4, TGF- beta 1 and alpha -SMA in 117 cases of cervical cancer, 48 cases of high grade squamous intraepithelial neoplasia (HSIL, CIN, 2 ~ 2) expression in 28 cases of chronic cervicitis tissues, and analyze the relationship between the expression and clinicopathological characteristics of patients with cervical cancer as well as the three table As the correlation, are helpful in the study of cervical cancer cells and TAFs interaction principle, so as to further explore the mechanism of invasion and metastasis of cervical cancer. Materials and methods: 1. subjects from the First Affiliated Hospital of Zhengzhou University Library in January January 2014 ~2015 pathological specimens of surgical resection in patients with cervical cancer tumor tissue (117 cases of all patients without chemotherapy), tissues of cervical lesions in patients with HSIL 48 cases were selected for cervical disease non hysterectomy patients of cervical tissue in 28 cases as control, 2 experienced experts in histopathology confirmed the diagnosis of.117 cases of cervical cancer patients: age 29~70 years old, the median age was 46 years; FIGO stage (2012) 67 cases of stage I, 50 stage II cases; squamous cell carcinoma 99 cases, 18 cases of adenocarcinoma; differentiation: G1 64 cases, G2 27 cases, G3 26 cases; 82 cases of interstitial infiltration depth: 1/2 quality, 35 cases of 1/2; lymph node metastasis: 21 No cases, 96 cases of.2. experimental methods: immunohistochemistry SP method in 3 specimens of CLIC4 group, the expression of TGF- beta 1 and alpha -SMA, to analyze the differences in expression between the 3 groups, explore the relationship between their expression and clinical pathological factors, and analysis the correlation of.3. expression between the three statistics are: the application of SPSS21.0 statistical software for statistical processing. Using X ~2 test, the positive rate between CLIC4, the correlation between the expression of TGF- beta 1 and alpha -SMA Spearman using.P0.05 rank correlation analysis for the difference was statistically significant. The expression of 1.CLIC4 in cervical cancer, the positive expression of CIN and chronic cervicitis tissues were respectively 76.92%, 45.83% expression of CLIC4 and 10.71%. in cervical carcinoma was higher than that of CIN and chronic cervicitis, the difference was statistically significant (P0.05). The expression of CLIC4 in cervical carcinoma with lymph node metastasis (2=4.84, P=0.04) and depth of stromal invasion (2=8.48, P=0.009), FIGO Staging (2=8.41, P=0.001), and the degree of differentiation (2=2.50, P=0.12), age (2=0.33, P=0.66), histological type (2=1.08, P=0.37) independent of.2.TGF- beta 1 in cervical carcinoma positive expression rate was 70.08%, the expression rate of HSIL was 47.91%. In chronic cervicitis for the expression of 17.85%. in cervical cancer TGF- beta 1 was higher than that of HSIL group, the difference was statistically significant (P0.05), the expression of TGF- beta 1 is higher than the rate of cervicitis cervical cancer tissues, the difference was statistically significant (P0.05). The expression of TGF- and lymph node metastasis in 1 cervical cancer tissues (x 2=5.08, P=0.03) and depth of stromal invasion (2=10.85, P=0.001), FIGO stage (x 2=8.06, P=0.01), and age (2=0.03, P=0.60), differentiation (2=2.45, P=0.15), histological type (2=0.60, P=0.58) independent of.3. alpha positive expression of -SMA in cervical carcinoma rate 97.43%, the expression in HSIL tissue The positive rate was 47.91% in chronic cervicitis for the expression of 7.14%. in cervical cancer was higher than that of the alpha -SMA cervical intraepithelial neoplasia tissues, the difference was statistically significant (P0.05), the expression of -SMA in cervical cancer was higher than that of alpha cervicitis tissue, the difference was statistically significant (P0.05). The expression of alpha -SMA in cervical cancer with lymph node metastasis (2=14.08, P=0.001) and depth of stromal invasion (2=7.21, P=0.03), and age (2=0.23, P=0.80), FIGO stage (x 2=3.52, P=0.12), histological type (2=0.76, P=0.40), degree of differentiation (2=2.30, P=0.26) had a positive correlation the expression of CLIC4 and TGF- beta 1 independent.4. in cervical cancer tissues (r=0.625, P=0.001); there was a positive correlation between CLIC4 and alpha -SMA (r=0.624, P=0.001). Conclusion CLIC4 1. in cervical carcinoma, TGF- beta 1 and alpha -SMA in cervical cancer in high expression, with the progress of cervical lesions CLIC4, TGF- and alpha -SMA beta 1 The expression rate gradually increased, suggesting that CLIC4, TGF- beta 1 and alpha -SMA and cervical cancer related to the occurrence and development of.2. in cervical cancer CLIC4 and TGF- beta 1 expression and cervical carcinoma with lymph node metastasis, depth of stromal invasion, FIGO staging; alpha -SMA expression and lymph node metastasis in cervical cancer, interstitial the depth of invasion. CLIC4, TGF- beta 1 and alpha -SMA and cervical cancer invasion and metastasis.

【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.33
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本文编号：1698157