TOPOⅡ、ERCC1、MDR1、PTEN、Livin基因在上皮性卵巢癌中的表达及其临床意义
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摘要
目的:通过分析TOPOII、ERCC1、MDR1、PTEN、Livin在81例上皮性卵巢癌中的表达,探讨其与上皮性卵巢癌病理类型、临床分期、组织学分级、化疗耐药及预后的关系。
     方法:对81例上皮性卵巢癌患者的临床病理资料进行回顾性分析。应用SPSS13.0统计软件,采用Kaplan-Meier方法计算生存率并绘制生存曲线,log-rank检验进行生存率差异的单因素分析,多因素分析采用Cox回归模型,相关性分析采用Spearman等级相关,计数资料采用χ2检验,均以P<0.05为差异有统计学意义。
     结果:
     1不同年龄段组织学分级差异有统计学意义(P<0.05)。<55岁组组织学分级低;≥55岁组组织学分级高。
     2单因素分析:耐药相关基因TOPOII、ERCC1的表达、治疗方法、手术方式是影响上皮性卵巢癌预后的相关因素(P<0.05)。TOPOII、ERCC1高表达,手术辅以术后化疗,行肿瘤细胞减灭术和或淋巴结清扫者生存率高。多因素回归分析表明:病理类型、手术-病理分期、组织学分级、耐药相关基因TOPOII、ERCC1、MDR1、PTEN、Livin的表达、淋巴结清扫、淋巴结转移、手术范围、治疗方法均不是影响上皮性卵巢癌预后的独立危险因素。
     3耐药相关基因与上皮性卵巢癌组织学分级、病理类型、手术-病理分期及化疗耐药的关系
     TOPOII、ERCC1、MDR1、PTEN、Livin的表达在上皮性卵巢癌化疗耐药组与敏感组之间无明显统计学差异(P>0.05),在不同的组织学分级、病理类型、手术-病理分期中其表达无明显统计学差异(P>0.05)。
     4淋巴结转移相关临床病理因素比较,年龄、病理类型、组织学分级无明显统计学差异(P均>0.05)。
     5耐药相关基因表达的相关性
     TOPOII与ERCC1两者的表达具有负相关性(r=-0.447,P<0.001),TOPOII与MDR1两者的表达具有负相关性(r=-0.159,P<0.05),TOPOII与PTEN两者的表达具有负相关性(r=-0.775,P<0.001),TOPOII与Livin两者的表达具有负相关性(r=-0.476,P<0.001);ERCC1与MDR1的表达呈正相关(r=0.322,P<0.001),ERCC1与PTEN的表达呈负相关(r=-0.404,P<0.001),ERCC1与Livin的表达无相关性(r=-0.037,P=0.636);MDR1与PTEN的表达呈负相关(r=-0.681,P<0.001)、MDR1与Livin的表达呈负相关(r=-0.456,P<0.001);PTEN与Livin的表达呈正相关(r=0.369,P<0.001)。
     结论:
     1上皮性卵巢癌组织细胞分化与年龄相关,年轻者组织分化差。
     2耐药相关基因TOPOII、ERCC1的表达、治疗方法、手术范围是影响上皮性卵巢癌预后的相关危险因素。
     3病理类型、手术-病理分期、组织学分级、耐药相关基因TOPOII、ERCC1、MDR1、PTEN、Livin的表达、淋巴结清扫、淋巴结转移、手术范围、治疗方法均不是影响上皮性卵巢癌预后的独立危险因素。
     4耐药相关基因TOPOII、ERCC1、MDR1、PTEN、Livin的表达与上皮性卵巢癌的病理类型、手术-病理分期、组织学分级及化疗耐药与否无明显相关性。
     5组织学分级、年龄、病理类型不是淋巴结转移的危险因素。
     6上皮性卵巢癌中TOPOII与ERCC1、MDR1、PTEN、Livin的表达呈负相关; ERCC1与MDR1的表达呈正相关,与PTEN的表达呈负相关,与Livin的表达无相关性;MDR1与PTEN、Livin的表达呈负相关;PTEN与Livin的表达呈正相关。耐药相关基因TOPOII、ERCC1、MDR1、PTEN、Livin的不同表达在上皮性卵巢癌的发生发展中可能具有相互协同、相互拮抗的关系。
Objective: TO study the expressions of TOPOII,ERCC1,MDR1,PTEN and Livin in the epithelial ovarian cancer tissues.TO evaluate the relationship between their expressions and pathologic type,operation-pathological stage,histological grade,chemotherapy resistance and the prognosis of epithelial ovarian cancer.
     Methods: To analyze retrospectively the clinical information of 81 patients with epithelial ovarian cancer.
     SPSS 13.0 software package was used. Using Kaplan-Meier method to calculate Survival rates and draw survival curve. Univariate analysis between different Survivorship rates was estimated by log-rank test. Multiple regression analysis were assessed by Cox proportional hazards model. Dependablity analysis was estimated by Spearman rank correlation. Enumeration data were compared withχ2 test.A statistically significant difference was indicated by P<0.05.
     Results:
     1 There are significant differences in histological type between the different age groups (P<0.05). The≥55 group has well differentiated,while the <55group has countrary results.
     2 Univariate analysis revealed that the expressions of TOPOII and ERCC1,treatment modality,operation circumsciption are significantly associated with the overall-survival of patients in epithelial ovarian cancer. The prognosis of the patients who have high expressions of TOPOII and ERCC1,enforced operation associated with chemotherapy and have exterminated tumor cell and lymph node cleaning operation are better.
     Multivariate analysis revealeds that pathologic type,operation- pathological stage,histological grade,expressions of drug fast related gene TOPOII,ERCC1, MDR1,PTEN and Livin,lymph node cleaning,lymph node metastasis, operation circumsciption,treatment modality are not independent risk factors for the prognosis of epithelial ovarian cancer.
     3 Relationship between drug fast related gene and pathologic type, operation- pathological stage,histological grade,chemotherapy resistance of epithelial ovarian cancer.
     There are no significant differences in the expressions of drug fast related gene TOPOII,ERCC1,MDR1,PTEN,Livin between chemotherapy resistance group and chemotherapy Sensitive group(P>0.05).And there are no significant differences between their expressions and different pathologic type,operation-pathological stage,histological grade(P>0.05).
     4 Comparison of various clinicopathologic factor related to lymph node metastasis,there are not significant differences in age,histological grade,pathologic type,operation-pathological stage(P>0.05).
     5 Correlation between the expressions of these drug fast related gene
     The expressions between TOPOII and ERCC1 shows negative correlation(r=-0.447,P<0.001),the expressions between TOPOII and MDR1 shows negative correlation(r=-0.159,P<0.05),the expressions between TOPOII and PTEN shows negative correlation(r=-0.775,P<0.001),the expressions between TOPOII and Livin shows negative correlation(r=-0.476,P<0.001);the expressions between ERCC1 and MDR1 shows positive correlation(r=0.322,P<0.001);the expressions between ERCC1 and PTEN shows negative correlation(r=-0.404,P<0.001);the expressions between ERCC1 and Livin shows no correlation(r=-0.037,P=0.636>0.05);the expressions between MDR1 and PTEN shows negative correlation(r=-0.681,P<0.001 ) ;the expressions between MDR1 and Livin shows negative correlation(r=-0.456,P<0.001);the expressions between PTEN and Livin shows positive correlation(r=0.369,P<0.001).
     Conclusion:
     1 Histological grade is correlated with the patient's age in epithelial ovarian cancer,when the patient's age is lower,the histological grade is worse.
     2 The expressions of TOPOII and ERCC1,treatment modality,operation circumsciption are correlative risk factors for the prognosis of epithelial ovarian cancer.
     3 Pathologic type,operation-pathological stage,histological grade,expressions of drug fast related gene TOPOII,ERCC1,MDR1,PTEN and Livin, lymph node cleaning,lymph node metastasis,operation circumsciption,treatment modality are not independent risk factors for the prognosis of epithelial ovarian cancer.
     4 Expressions of drug fast related gene TOPOII,ERCC1,MDR1,PTEN and Livin are not significantly correlated with the pathologic type, operation- pathological stage,histological grade and chemotherapy resistance of epithelial ovarian cancer.
     5 Histological grade,age and pathologic type are not risk facors for lymph node metastasis in epithelial ovarian cancer.
     6 In epithelial ovarian cancer,the expressions between TOPOII and ERCC1, MDR1,PTEN,Livin shows negative correlation;the expressions between ERCC1 and MDR1 shows positive correlation;the expressions between ERCC1 and PTEN shows negative correlation;the expressions between ERCC1 and Livin shows no correlation;the expressions between MDR1 and PTEN,Livin shows negative correlation;the expressions between PTEN and Livin shows positive correlation.
     The different expressions of TOPOII,ERCC1,MDR1,PTEN and Livin may produce a cooperation or antagonistic effect with the development of epithelial ovarian cancer tissues.
引文
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