STC-2在宫颈癌表达的功能研究及其临床意义

发布时间：2018-04-21 14:40

  本文选题：斯钙素2 + 表达　； 参考：《南京医科大学》2016年博士论文

【摘要】：研究背景：宫颈癌是女性最常见的生殖系统恶性肿瘤,其发病率和死亡率在全球女性恶性肿瘤中均位列第4。探索敏感、有效的宫颈癌生物标记,以协助诊断、指导治疗及预测疗效,是肿瘤临床诊治的一项重点。斯钙素-2(stanniocalcin 2, STC2)是一类糖蛋白激素,在人体组织中有广泛表达,参与调节多种生理、病理过程。近年的系列研究表明,STC2与多种肿瘤的发生、发展存在密切关联。但是有关STC2与宫颈癌临床病理因素的相关性,及能否预测宫颈癌的放疗疗效,目前尚无明确结论。本研究试图通过样本检测、细胞株实验和宫颈癌临床病理参数分析及放疗后生存期随访,验证STC2在肿瘤组织的表达及其临床意义,观察STC2表达与宫颈癌细胞株增殖、迁移和侵袭的关联,并评估STC2在宫颈癌放疗疗效方面的预测价值。目的：评估STC2在宫颈癌的表达状况,分析其表达对肿瘤细胞功能的影响,以及对于宫颈癌患者的临床意义。方法：(1)收集50例宫颈癌肿瘤标本,采用荧光定量PCR的方法检测宫颈癌以及癌旁正常组织中STC2 mRNA的表达情况;采用western blot法检测宫颈癌组织以及相应癌旁正常组织中STC2蛋白的表达情况；分析宫颈癌组织中STC2的表达与宫颈癌患者临床病理因素的相关性。(2)将si-STC2转染宫颈癌Hela细胞株以沉默细胞中STC2的表达。对转染后的Hela细胞株用western blot法检测STC2蛋白的表达情况,并用CCK-8法检测其增殖能力,用Transwe Ⅱ小室法检测转染后Hela细胞的侵袭性,用细胞划痕实验评估转染si-STC2对Hela细胞迁移性的影响。(3)收集本院自2004～2007年期间诊治的,共92例宫颈癌病理组织标本,记录临床病理参数,进行放疗后生存随访平均5年。检测宫颈癌以及癌旁正常组织中STC2 mRNA及蛋白的表达情况；统计分析STC2表达与宫颈癌患者临床病理参数之间的相关性；用Kaplan-Meier生存曲线,对STC2表达与放疗后患者的总生存期(overall survival, OS)及无疾病进展生存期(progress free survival, PFS)进行相关分析；用Cox比例风险回归模型对独立预后因子进行多因素回归分析。结果：(1)宫颈癌组织中的STC2 mRNA和蛋白表达显著高于正常组织；STC2的表达与宫颈癌患者年龄、FIGO分期、肿瘤大小、病理分化程度、病理鳞癌／腺癌无明显关联,而与淋巴结转移有关(尸=0.0020.01)。(2)下调STC2基因后Hela细胞的增殖、侵袭以及迁移能力减弱。(3)STC2在宫颈癌肿瘤组织高表达患者放疗后的OS(P=0.0130.05)和PFS(P=0.0040.01)均较低表达者短；另外淋巴结转移患者的OS较短(P=0.0350.05)。结论：(1) STC2 mRNA和蛋白在宫颈癌组织的表达显著高于正常组织；(2)STC2能够促进宫颈癌Hela细胞的增殖、侵袭和转移；(3)STC2表达与宫颈癌患者的淋巴结转移相关；(4)STC2表达与宫颈癌患者的OS和PFS呈显著负相关。
[Abstract]:Background: cervical cancer is the most common malignant tumor of the reproductive system in women. To explore sensitive and effective biomarkers for diagnosis, treatment and prognosis of cervical cancer is an important point in clinical diagnosis and treatment of cancer. Statin-2 stanniocalcin 2 (STC2) is a kind of glycoprotein hormone, which is widely expressed in human tissues and participates in many physiological and pathological processes. A series of studies in recent years have shown that STC2 is closely related to the occurrence and development of many kinds of tumors. However, there is no clear conclusion about the correlation between STC2 and clinicopathological factors of cervical cancer, and whether it can predict the curative effect of radiotherapy for cervical cancer. The purpose of this study was to verify the expression of STC2 in tumor tissue and its clinical significance, and to observe the expression of STC2 and the proliferation of cervical cancer cell line by means of sample detection, cell line test, clinicopathologic parameters analysis and survival follow-up after radiotherapy. Relationship between migration and invasion, and evaluation of STC2 in predicting the efficacy of radiotherapy for cervical cancer. Aim: to evaluate the expression of STC2 in cervical cancer, and to analyze its effect on tumor cell function and its clinical significance. Methods 50 specimens of cervical carcinoma were collected. The expression of STC2 mRNA in cervical carcinoma and adjacent normal tissues was detected by fluorescence quantitative PCR. Western blot method was used to detect the expression of STC2 protein in cervical carcinoma tissues and adjacent normal tissues. To analyze the correlation between the expression of STC2 and the clinicopathological factors of cervical carcinoma. (2) transfection of si-STC2 into cervical cancer Hela cell line to silence the expression of STC2 in cervical cancer cells. After transfection, the expression of STC2 protein was detected by western blot assay, the proliferative ability was detected by CCK-8 assay, and the invasiveness of Hela cells after transfection was detected by Transwe 鈪，

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