CTHRC1在肾细胞癌中的表达及其临床相关预后分析

发布时间：2018-04-18 11:00

本文选题：CTHRC1 + 肾细胞癌　；参考：《天津医科大学》2014年硕士论文

【摘要】：目的：肾细胞癌(renal cell carcinoma, RCC)是泌尿系统常见的恶性肿瘤之一,其起病常常隐匿,常无典型的临床表现,早期诊断率不高,很多患者发现时已是中晚期,并且其中30%的患者在诊断时已发生转移,失去手术的机会。另外手术后的复发率仍高达20%～40%。但治疗方面RCC对于放化疗均不敏感,免疫治疗所导致的严重不良反应也阻碍了其广泛的临床应用。虽然近年来多种靶向药物治疗肾癌,尤其中晚期肾癌的研究取得了可喜的成果,但部分患者对靶向治疗药物仍无效,RCC的新的分子生物标记物及靶向治疗方法尚需要进一步探索。本研究旨在研究CTHRC1(Collagen triple helix repeat containing-1)在肾癌组织及癌旁组织中的表达情况,分析CTHRC1在RCC表达情况与临床病理学因素之间的相关性。并探讨其临床意义及CTHRC1基因是否可作为RCC分子生物标记物,进而为RCC基因水平断和治疗的临床应用奠定实验基础。方法：首先运用免疫组织化学方法分析73例RCC组织和20例癌旁正常组织中CTHRC1蛋白的表达情况,确定差异表达是否具有统计学意义,并分析CTHRC1在RCC表达情况与临床病理学因素(性别、年龄、病理T分期、Fuhrman分级、转移等)之间的是否存在关联。之后运用western blot技术进一步检测CTHRC1蛋白在8对RCC组织和癌旁正常组织中的表达情况。最后随访患者后采用Kaplan-Meier绘制生存曲线进行Log-rank检验性,确定CTHRC1对患者生存期是否有影响。同时进行COX单因素及多因素回归分析,评估可能对RCC患者预后有影响的危险因素。结果： 1.CTHRC1在肿瘤组织中的表达阳性率为37.0%(27/73),明显低于癌旁正常组织的阳性表达率90%(18/20),差异具有统计学意义CP0.05)。CTHRC1在RCC组织中与患者性别、年龄、肿瘤大小、肿瘤位置、Fuhrman分级、肿瘤坏死等之间差异无统计学意义(P0.05),而其表达在肿瘤病理T分期之间的差异具有统计学意义(P0.05)。 2. western blot实验分析显示8例RCC肿瘤组织CTHRC1表达量均明显弱于癌旁正常组织。其结果与免疫组织化学一致,进一步验证了CTHRC1蛋白在肿瘤组织表达要弱于癌旁正常组织。 3. Kaplan-Meier法绘制生存曲线显示CTHRC1蛋白阳性表达者患者生存期高于阴性表达患者((Log-rank,P=0.027),提示在肾细胞癌患者中CTHRC1高表达可能对患者生存期是一种有利因素。 4.COX回归单因素结果显示CTHRC1表达、病理T分期、Fuhrman分级、转移对患者预后有影响(P0.05)。进一步行多因素分析示CTHRC1表达、Fuhrman分级、转移三者为影响患者预后的独立危险因素(P0.05)。结论： 1.CTHRC1在肾癌组织中表达要低于癌旁正常组织,且其表达水平随着肿瘤病理分期的增加而降低,提示CTHRC1可能具有抑制肿瘤生长的作用以及其在肿瘤的发生、进展中发挥作用。 2.采用Kaplan-Meier方法分析绘制CTHRC1相关的生存曲线,在CTHRC1高表达患者的生存率高于CTHRC1低表达患者。CTHRC1对患者生存期有影响,提示其为肾细胞癌患者预后影响因素。 3.COX回归单因素分析显示：CTHRC1蛋白表达、病理T分期、Fuhrman分级、转移情况是对预后有意义的影响因子。多因素分析最终结果显示：CTHRC1蛋白表达、Fuhrman分级、转移3个因素是影响患者预后的独立因素。CTHRC1可能成为肾细胞癌新的分子生物学预后标记物及基因治疗的有效靶点,具有潜在的临床应用价值,为进一步的临床研究打下了实验基础。
[Abstract]:Purpose :

Renal cell carcinoma ( RCC ) is one of the most common malignant tumors in the urinary system .

Method :

We analyzed the expression of CTHRC1 protein in 73 RCC tissues and 20 normal tissues by immunohistochemical method . The expression of CTHRC1 in RCC tissues and adjacent normal tissues was determined by western blot .

Results :

1 . The positive rate of CTHRC1 expression in tumor tissues was 37.0 % ( 27 / 73 ) , which was significantly lower than that of normal tissue ( 90 % ( 18 / 20 ) . The difference was statistically significant ( CP0 . 05 ) . There was no significant difference between CTHRC1 and sex , age , tumor size , tumor location , Fuhrman grade , tumor necrosis and so on in RCC tissues ( P0.05 ) .

2 . Western blot analysis showed that the expression of CTHRC1 was significantly weaker than normal tissues in 8 RCC tumor tissues . The results showed that the expression of CTHRC1 protein in tumor tissues was weaker than that of normal tissues .

3 . Kaplan - Meier method for survival curves showed that the survival time of patients with CTHRC1 positive expression was higher than that in patients with negative expression ( Log - rank , P = 0.027 ) , suggesting that high expression of CTHRC1 in patients with renal cell carcinoma may be a favorable factor for the survival of patients .

4 . COX regression analysis showed that the expression of CTHRC1 , pathological T stage , Fuhrman grade and metastasis had an influence on the prognosis of patients ( P0.05 ) .

Conclusion :

1 . The expression level of CTHRC1 is lower than that of normal tissue in renal cell carcinoma , and its expression level decreases with the increase of pathological stage of tumor , suggesting that CTHRC1 may play a role in inhibiting tumor growth and its role in carcinogenesis and progression of tumor .

2 . Kaplan - Meier method was used to analyze the survival curves associated with CTHRC1 . The survival rate of CTHRC1 was higher than that of CTHRC1 . CTHRC1 had an influence on the survival of patients and suggested that it was a prognostic factor for patients with renal cell carcinoma .

3 . COX regression single factor analysis showed that CTHRC1 protein expression , pathological T stage , Fuhrman classification and metastasis were the prognostic factors . The results of multivariate analysis showed that CTHRC1 protein expression , Fuhrman grade and metastasis were independent factors which influence the prognosis of patients . CTHRC1 might be a new molecular biological prognostic marker for renal cell carcinoma and the effective target of gene therapy . It has potential clinical application value and lays an experimental foundation for further clinical research .

【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.11

【参考文献】