【作者】 刘丽爽；

【导师】 杨波；

【作者基本信息】 河北医科大学 ， 妇产科学， 2017， 硕士

【摘要】 目的:卵巢上皮性肿瘤(Epithelial ovarian tumor)是女性常见生殖器肿瘤之一,是影响女性生命及生活质量的疾病之一,包括良性、交界性和恶性。而卵巢上皮性恶性肿瘤(Epithelial ovarian cancer,EOC)是常见妇科恶性肿瘤之一,其病死率居女性肿瘤中的第5位。微小核糖核酸(Micro RNA,miRNA)是一类长约19~24nt的非编码小RNA,在转录后水平调节基因的表达。在很多生物学过程,包括肿瘤发生发展、侵袭与转移、耐药和复发等过程中均可发现miRNA的表达。本实验检测初治卵巢上皮性癌原发灶、初治卵巢上皮性癌转移灶、复发卵巢上皮性癌和卵巢上皮性良性肿瘤组织中,miRNA-3198、miRNA-8084、miRNA-7515和miRNA-3613-3P四种miRNA的表达情况,比较各组表达差异,并探讨其可能的机制,以期发现miRNA在卵巢上皮性癌的发生、侵袭与转移及复发中的作用,为卵巢上皮性癌的诊治提供新的方向。方法:1无菌条件下收集在白求恩国际和平医院从2010年10月至2016年11月手术的临床组织标本,共60例,包括初治卵巢上皮性癌原发灶组织(A组)15例、初治卵巢上皮性癌转移灶组织(B组)15例、复发卵巢上皮性癌组织(C组)16例和卵巢上皮性良性肿瘤组织(D组)14例。所有组织标本置于-80℃冰箱冷藏。初治卵巢上皮性癌所有患者手术前均未行任何相关手术及辅助治疗。复发卵巢上皮性癌所有患者满足二次减灭术的适应症:距离最后一次化疗结束后复发间隔时间6~12个月;肿瘤病灶孤立且可完整切除;无腹水。所有标本均有术后病理确诊。2实时荧光定量聚合酶链式反应(Quantitative Real-time polymerase chain reaction,q RT-PCR)检测并用统计学方法分析结果。结果:1 miRNA-3198在A、B、C和D四组中表达情况的比较:A、B、C和D四组miRNA-3198的表达水平不全相同,具有统计学差异(χ2=20.32,P<0.001)。进一步进行两两比较,结果是:B组miRNA-3198的表达水平与其余三组均不相同,均具有统计学差异(P<0.05),B组是四组中miRNA-3198表达水平最低的一组。另外,A组低于D组,具有统计学差异(P<0.05);C组低于D组,具有统计学差异(P<0.05)。D组是四组中miRNA-3198表达水平最高的一组。而A组与C组的表达水平无统计学差异(P>0.05)。2 miRNA-7515在A、B、C和D四组中表达情况的比较:A、B、C和D四组miRNA-7515的表达水平不全相同,具有统计学差异(χ2=19.23,P<0.001)。进一步进行两两比较,结果是:A、B、C三组miRNA-7515的表达水平与D组均不相同,均具有统计学差异(P<0.05),D组是四组中miRNA-7515表达水平最高的一组,而A、B、C三组miRNA-7515的表达水平无统计学差异(P>0.05)。3 miRNA-8084在A、B、C和D四组中表达情况的比较:A、B、C和D四组miRNA-8084的表达水平不全相同,具有统计学差异(χ2=18.70,P<0.001)。进一步进行两两比较,结果是:A、B、C三组miRNA-8084的表达水平与D组均不相同,均具有统计学差异(P<0.05),D组是四组中miRNA-8084表达水平最高的一组,而A、B、C三组miRNA-8084的表达水平无统计学差异(P>0.05)。4 miRNA-3613-3P在A、B、C和D四组中表达情况的比较:A、B、C和D四组miRNA-3613-3P的表达水平不全相同,具有统计学差异(χ2=17.81,P<0.001)。进一步进行两两比较,结果是:B组和C组中miRNA-3613-3P的表达水平均低于A组,具有统计学差异(P<0.05)。B组和C组miRNA-3613-3P的表达水平均低于D组,具有统计学差异(P<0.05)。而A组和D组miRNA-3613-3P的表达水平无统计学差异(P>0.05),B组和C组miRNA-3613-3P的表达水平无统计学差异(P>0.05)。结论:1 miRNA-3198在初治卵巢上皮性癌原发灶、初治卵巢上皮性癌转移灶和复发卵巢上皮性癌组织中均为低表达,在初治卵巢上皮性癌转移灶组织中的表达水平最低,可能参与卵巢癌的发生发展、转移及复发。2 miRNA-7515在初治卵巢上皮性癌原发灶、初治卵巢上皮性癌转移灶和复发卵巢上皮性癌组织中均为低表达,可能参与卵巢癌的发生。3 miRNA-8084在初治卵巢上皮性癌原发灶、初治卵巢上皮性癌转移灶和复发卵巢上皮性癌组织中均为低表达,可能参与卵巢癌的发生。4 miRNA-3613-3P在初治卵巢上皮性癌转移灶和复发卵巢上皮性癌组织中均为低表达,可能参与卵巢癌的转移与复发。更多还原

【Abstract】 Objective: Epithelial ovarian tumor is one of the most common female genital tumor.It poses a threat to female health and the quality of life,including benign,borderline and malignant tumor.Epithelial ovarian cancer(EOC)is one of the most common gynecologic malignant tumor,it is the fifth leading cause of cancer-related deaths in women.Micro RNA(miRNAs)are short non-coding RNA molecules of 19-24 nucleotides(nt)involved in post-transcriptional regulation of genes expression.Mi RNA have been shown to play an important role in diverse biological processes,including tumor genesis,tumor development,invasion,metastasis,drug resistance and relapse of tumor.The purpose of the present study was to assess the differential expression of micro RNA-3198,micro RNA-7515,micro RNA-3613-3P and micro RNA-8084 between primary ovarian cancer,ovarian cancer metastases,recurrent epithelial ovarian cancer and epithelial ovarian benign tumor tissues,and to explore the possible mechanism.In order to find a new direction for the diagnosis and treatment of epithelial ovarian cancer,this study need to explore the role of the four miRNA in diverse biological processes,including epithelial ovarian cancer genesis,tumor development,invasion,metastasis,drug resistance and relapse of epithelial ovarian cancer.Methods:1 A total of 60 fresh-frozen epithelial ovarian tumor tissues were collected at the Department of Bethune International Peace Hospital from October 2010 to November 2016 in rigorously aseptic conditions,including 15 primary ovarian cancer tissues(group A),15 ovarian cancer metastases tissues(group B),16 recurrent epithelial ovarian cancer tissues(group C)and 14 epithelial ovarian benign tumor tissues(group D).The samples werefresh-frozen in-80℃ immediately.The patients with primary ovarian cancer had not received any local or systemic anticancer treatments prior to the surgery.Secondary cytoreductive surgery can be considered for patients who recur after a long disease-free interval(6 months or more),isolated tumor lesions and can complete resection and without ascites.All of the epithelial ovarian tumor tissues were histologically examined.2 Total miRNA was extracted from primary ovarian cancer,ovarian cancer metastases,recurrent epithelial ovarian cancer and epithelial ovarian benign tumor tissues and miRNA expression levels were confirmed by Quantitative Real-time polymerase chain reaction(q RT-PCR).Expression levels were compared between the four groups and analyzed statistically.Results:1 The levels of miRNA-3198 expression in four groups,group A,B,C and D were compared:The levels of miRNA-3198 expression in the four groups were different,they had statistical significance(χ2=20.32,P<0.001).The results were further compared.The levels of miRNA-3198 expression between group B and group A,C,D were different,they had statistical significance(P<0.05),and the miRNA-3198 expression levels of group B was lower than other three.The miRNA-3198 expression levels of group A was lower than group D,they had statistical significance(P<0.05).The miRNA-3198 expression levels of group C was lower than group D,they had statistical significance(P<0.05).The miRNA-3198 expression levels of group D was higher than other three.The levels of miRNA-3198 expression between group A and group C were no different,they had no statistical significance(P>0.05).2 The levels of miRNA-7515 expression in four groups,group A,B,C and D were compared:The levels of miRNA-7515 expression in four groups were different,they had statistical significance(χ2=19.23,P<0.001).The results were further compared.The levels of miRNA-7515 expression between group A,B,C and group D were different,they had statistical significance(P<0.05),and themiRNA-7515 expression levels of group D was higher than other three.But the levels of miRNA-7515 expression between group A,B and group C were no different,they had no statistical significance(P>0.05).3 The levels of miRNA-8084 expression in four groups,group A,B,C and D were compared:The levels of miRNA-8084 expression in four groups were different,they had statistical significance(χ2=18.70,P<0.001).The results were further compared.The levels of miRNA-8084 expression between group A,B,C and group D were different,they had statistical significance(P<0.05),and the miRNA-8084 expression levels of group D was higher than other three.But the levels of miRNA-8084 expression between group A,B and group C were no different,they had no statistical significance(P>0.05).4 The levels of miRNA-3613-3P expression in four groups,group A,B,C and D were compared:The levels of miRNA-3613-3P expression in four groups were different,they had statistical significance(χ2=17.81,P<0.001).The results were further compared.The miRNA-3613-3P expression levels of group B,C were lower than group A,they had statistical significance(P<0.05).The miRNA-3613-3P expression levels of group B,C were lower than group D,they had statistical significance(P<0.05).But the levels of miRNA-3613-3P expression between group A and group D were no different,they had no statistical significance(P>0.05).The levels of miRNA-3613-3P expression between group B and group C were no different,they had no statistical significance(P>0.05).Conclusions:1 The miRNA-3198 expression levels of primary ovarian cancer,ovarian cancer metastases and recurrent epithelial ovarian cancer tissues was lower than another.Ovarian cancer metastases tissues was lower than other three.miRNA-3198 may be involved in epithelial ovarian tumor genesis,tumor development,invasion,metastasis and relapse of epithelial ovarian cancer.2 The miRNA-7515 expression levels of primary ovarian cancer,ovarian cancer metastases and recurrent epithelial ovarian cancer tissues was lowerthan another.Mi RNA-7515 may be involved in the development of ovarian cancer.3 miRNA-8084 expression levels of primary ovarian cancer,ovarian cancer metastases and recurrent epithelial ovarian cancer tissues was lower than another.Mi RNA-8084 may be involved in the development of ovarian cancer.4 The miRNA-3613-3P expression levels of ovarian cancer metastases and recurrent epithelial ovarian cancer tissues were lower than other two.Mi RNA-3613-3P may be involved in the tumor metastasis and recurrence of ovarian cancer.更多还原