肿瘤研究与临床
腫瘤研究與臨床
종류연구여림상
CANCER RESEARCH AND CLINIC
2013年
10期
663-668
,共6页
卵巢上皮癌%活性氧%乏氧诱导因子-1α%氧代谢
卵巢上皮癌%活性氧%乏氧誘導因子-1α%氧代謝
란소상피암%활성양%핍양유도인자-1α%양대사
Epithelial ovarian cancer%Reactive oxygen species%Hypoxia-inducible factor-1α%Oxygen metabolism
目的 检测卵巢上皮癌组织中乏氧诱导因子-1α(HIF-1α)mRNA、蛋白以及活性氧(ROS)的表达,探讨卵巢上皮癌组织中氧代谢的异常,以及两者在卵巢上皮癌发生发展中的相互作用.方法 应用实时RT-PCR法和免疫组织化学Elivision plus二步法分别测定卵巢上皮癌组织中HIF-1αmRNA及蛋白的表达；应用DCFH-DA法检测组织中ROS的表达.结果 卵巢上皮癌组织HIF-1 αmRNA相对含量(4.466±0.754)明显高于良性卵巢肿瘤(6.073±1.053)(t=-7.701,P=0.000),良性卵巢肿瘤、早期(5.048±0.645)及晚期卵巢上皮癌(4.146 ±0.632)HIF-1α mRNA表达呈递增趋势(t=5.301,P=0.000)；HIF-1α mRNA表达与组织学分级及淋巴结转移呈正相关(t=3.724、-3.851,均P=0.000).HIF-1 α蛋白在卵巢上皮癌组织中阳性表达率[63.49％(40/63)1明显高于良性对照[36.36％(8/22)](U=433,P=0.005),HIF-1 α蛋白阳性表达率与淋巴结转移及临床分期呈正相关(x2=4.289、12.360,P=0.038、0.000).卵巢上皮癌组织中ROS表达水平为110.239±18.414,较良性对照(58.366±20.360)明显升高(t=11.068,P=0.000)；ROS表达与卵巢上皮癌组织学分级、淋巴结转移及临床分期呈正相关(t=-2.055、2.816、-4.138,P=0.044、0.007、0.000).在卵巢上皮癌组织中HIF-1 α蛋白表达与ROS呈中度正相关(r=0.572,P=0.000)；在中低分化组及晚期组中两者呈中度正相关(r=0.540,P=O.002;r=0.572,P=0.000)；在淋巴结转移组中两者呈高度正相关(r=0.703,P=0.001)；HIF-1α mRNA与ROS表达呈低度相关(r=0.376,P=0.002).结论 乏氧是卵巢上皮癌的基本特征,随着肿瘤进展乏氧程度逐渐加重；HIF-1α的异常表达与卵巢上皮癌潜在的恶性生物学行为密切相关,可能影响卵巢上皮癌预后.在乏氧状态下,ROS与HIF-1 α可能参与肿瘤的发生过程.在卵巢上皮癌侵袭转移过程中,ROS对HIF-1α的正向调节可能发挥重要作用.肿瘤乏氧状态下,ROS对HIF-1 α的调节可以发生在转录和蛋白等水平,主要是蛋白水平的改变.
目的 檢測卵巢上皮癌組織中乏氧誘導因子-1α(HIF-1α)mRNA、蛋白以及活性氧(ROS)的錶達,探討卵巢上皮癌組織中氧代謝的異常,以及兩者在卵巢上皮癌髮生髮展中的相互作用.方法 應用實時RT-PCR法和免疫組織化學Elivision plus二步法分彆測定卵巢上皮癌組織中HIF-1αmRNA及蛋白的錶達；應用DCFH-DA法檢測組織中ROS的錶達.結果 卵巢上皮癌組織HIF-1 αmRNA相對含量(4.466±0.754)明顯高于良性卵巢腫瘤(6.073±1.053)(t=-7.701,P=0.000),良性卵巢腫瘤、早期(5.048±0.645)及晚期卵巢上皮癌(4.146 ±0.632)HIF-1α mRNA錶達呈遞增趨勢(t=5.301,P=0.000)；HIF-1α mRNA錶達與組織學分級及淋巴結轉移呈正相關(t=3.724、-3.851,均P=0.000).HIF-1 α蛋白在卵巢上皮癌組織中暘性錶達率[63.49％(40/63)1明顯高于良性對照[36.36％(8/22)](U=433,P=0.005),HIF-1 α蛋白暘性錶達率與淋巴結轉移及臨床分期呈正相關(x2=4.289、12.360,P=0.038、0.000).卵巢上皮癌組織中ROS錶達水平為110.239±18.414,較良性對照(58.366±20.360)明顯升高(t=11.068,P=0.000)；ROS錶達與卵巢上皮癌組織學分級、淋巴結轉移及臨床分期呈正相關(t=-2.055、2.816、-4.138,P=0.044、0.007、0.000).在卵巢上皮癌組織中HIF-1 α蛋白錶達與ROS呈中度正相關(r=0.572,P=0.000)；在中低分化組及晚期組中兩者呈中度正相關(r=0.540,P=O.002;r=0.572,P=0.000)；在淋巴結轉移組中兩者呈高度正相關(r=0.703,P=0.001)；HIF-1α mRNA與ROS錶達呈低度相關(r=0.376,P=0.002).結論 乏氧是卵巢上皮癌的基本特徵,隨著腫瘤進展乏氧程度逐漸加重；HIF-1α的異常錶達與卵巢上皮癌潛在的噁性生物學行為密切相關,可能影響卵巢上皮癌預後.在乏氧狀態下,ROS與HIF-1 α可能參與腫瘤的髮生過程.在卵巢上皮癌侵襲轉移過程中,ROS對HIF-1α的正嚮調節可能髮揮重要作用.腫瘤乏氧狀態下,ROS對HIF-1 α的調節可以髮生在轉錄和蛋白等水平,主要是蛋白水平的改變.
목적 검측란소상피암조직중핍양유도인자-1α(HIF-1α)mRNA、단백이급활성양(ROS)적표체,탐토란소상피암조직중양대사적이상,이급량자재란소상피암발생발전중적상호작용.방법 응용실시RT-PCR법화면역조직화학Elivision plus이보법분별측정란소상피암조직중HIF-1αmRNA급단백적표체；응용DCFH-DA법검측조직중ROS적표체.결과 란소상피암조직HIF-1 αmRNA상대함량(4.466±0.754)명현고우량성란소종류(6.073±1.053)(t=-7.701,P=0.000),량성란소종류、조기(5.048±0.645)급만기란소상피암(4.146 ±0.632)HIF-1α mRNA표체정체증추세(t=5.301,P=0.000)；HIF-1α mRNA표체여조직학분급급림파결전이정정상관(t=3.724、-3.851,균P=0.000).HIF-1 α단백재란소상피암조직중양성표체솔[63.49％(40/63)1명현고우량성대조[36.36％(8/22)](U=433,P=0.005),HIF-1 α단백양성표체솔여림파결전이급림상분기정정상관(x2=4.289、12.360,P=0.038、0.000).란소상피암조직중ROS표체수평위110.239±18.414,교량성대조(58.366±20.360)명현승고(t=11.068,P=0.000)；ROS표체여란소상피암조직학분급、림파결전이급림상분기정정상관(t=-2.055、2.816、-4.138,P=0.044、0.007、0.000).재란소상피암조직중HIF-1 α단백표체여ROS정중도정상관(r=0.572,P=0.000)；재중저분화조급만기조중량자정중도정상관(r=0.540,P=O.002;r=0.572,P=0.000)；재림파결전이조중량자정고도정상관(r=0.703,P=0.001)；HIF-1α mRNA여ROS표체정저도상관(r=0.376,P=0.002).결론 핍양시란소상피암적기본특정,수착종류진전핍양정도축점가중；HIF-1α적이상표체여란소상피암잠재적악성생물학행위밀절상관,가능영향란소상피암예후.재핍양상태하,ROS여HIF-1 α가능삼여종류적발생과정.재란소상피암침습전이과정중,ROS대HIF-1α적정향조절가능발휘중요작용.종류핍양상태하,ROS대HIF-1 α적조절가이발생재전록화단백등수평,주요시단백수평적개변.
Objective To detect the expression of hypoxia inducible factor-lα (HIF-1α) in both mRNA and protein and reactive oxygen species (ROS) levels in human epithelial ovarian cancer,and investigate the abnormal state of oxygen metabolism and their interaction in human epithelial ovarian cancer develoment.Methods The expression of HIF-1α in mRNA and protein in epithelial ovarian cancer were detected by real time reverse transcription-polymerase chain reaction and immunohistochemical Elivision plus two-step method,and the level of ROS was detected by fluorescence microplate reader.Results The relative content of HIF-1α mRNA in the epithelial ovarian cancer group was 4.466±0.754,which was higher than that of the benign control group (6.073±1.053) (t =-7.701,P =0.000).The expression of HIF-1α mRNA was raised gradually in tissues of the benign ovarian tumor,early and advanced stage of epithelial ovarian cancer (t =5.301,P =0.000).The expression of HIF-1α mRNA in the epithelial ovarian cancer had positive correlation with grade and lymph node metastasis (t =3.724,-3.851,P =0.000).The positive expression rate of HIF-1 α protein in epithelial ovarian cancer was 63.49 ％ (40/63),which was higher than that of the benign group (U =433,P =0.005),which had positive correlation with lymph node metastasis and stage (x2 =4.289,12.360; P =0.038,0.000).The expression of ROS in the epithelial ovarian cancer was 110.239±18.414,which was higher than that of the benign group (58.366±20.360) (t =11.068,P =0.000),which had positive correlation with grade,lymph node metastasis and stage (t =-2.055,2.816,-4.138; P =0.044,0.007,0.000).There was a moderate positive correlation between the expression of HIF-1α mRNA and ROS in epithelial ovarian cancer (r =0.572,P =0.000),and that was similar in low differentiation group and advanced group,there was a relatively high positive correlation in lymph node metastasis group (r =0.703,P =0.001),there was a relatively low correlation between HIF-1α mRNA and ROS (r =0.376,P =0.002).Conclusion Hypoxia is the basic characteristic of human epithelial ovarian carcers.This study suggested that HIF-1α is associated with human epithelial overaian cancer prognosis.ROS and HIF-1α might be involved in the genesis of human epithelial ovarian cancer,and the regulation of ROS to HIF-1α may play the important roles in the invasion and metastasis process of human epithelial ovarian cancer.The expression of HIF-1α is regulated by ROS at the transcriptional and protein levels,probably mainly on protein level.
