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目的筛选在卵巢癌演进过程中起重要作用的microRNA(miRNA),检测关键miRNA与临床病理及预后的联系,找出与卵巢浆液性癌预后相关的miRNA。方法 miRNA芯片技术分别检测6例Ⅰ期浆液性癌,4例Ⅲ期浆液性癌的miRNA表达谱差异。统计分析,从中挑选4个miRNA,miR-510、miR-509-5p、miR-508-3p、miR-483-5p,采用实时定量PCR方法检测其在16例Ⅰ期浆液性癌、35例Ⅲ期浆液性癌中的表达,对比分析。收集验证组患者的临床病理及预后资料。将miRNA实时定量PCR结果分为高表达组和低表达组,分别统计各miRNA的表达与临床病理参数及预后的关系。结果 miRNA芯片技术分析了768个miRNA在Ⅰ期和Ⅲ期的表达谱,其中26个miRNA在两组中的表达具有显著差异(P<0.05),差别在两倍以上。对比Ⅰ期,Ⅲ期中6个miRNA上调,20个miRNA下调。实时定量PCR结果与miRNA芯片结果一致,显示miR-510、miR-509-5p、miR-508-3p在Ⅰ期卵巢癌标本中显著高于Ⅲ期浆液性癌,miR-483在Ⅰ期中表达显著低于Ⅲ期浆液性卵巢癌。但4个miRNA的表达与其他临床病理参数无关。生存分析发现miR-510、miR-509-5p二者与预后有关,高表达组的预后显著优于低表达组。结论 miRNA参与卵巢浆液性癌的发展,miR-510及miR-509-5p可能在卵巢癌的侵袭和转移中起作用,有望成为预测卵巢癌预后的分子标记物。
Objective To screen microRNAs (miRNAs) that play an important role in the evolution of ovarian cancer, to detect the relationship between the key miRNAs and clinical pathology and prognosis, and to identify miRNAs related to prognosis of ovarian serous carcinoma. Methods miRNA microarray technique was used to detect the miRNA expression profiles of 6 cases of stage Ⅰ serous carcinoma and 4 cases of stage Ⅲ serous carcinoma respectively. Four miRNAs, miR-510, miR-509-5p, miR-508-3p and miR-483-5p were selected and analyzed by real-time quantitative polymerase chain reaction in 16 cases of stage Ⅰ serous carcinoma, 35 cases of stage Ⅲ Stage serous carcinoma, comparative analysis. The patients in the validation group were collected for clinical pathology and prognosis. The miRNA real-time quantitative PCR results were divided into high expression group and low expression group, respectively, the expression of each miRNA and clinicopathological parameters and prognosis. Results miRNA microarray was used to analyze the expression profiles of 768 miRNAs in stages I and III. The expression of 26 miRNAs was significantly different between the two groups (P <0.05), with a difference of more than twice. Compared with stage Ⅰ, stage Ⅲ, 6 miRNAs were up-regulated and 20 miRNAs were down-regulated. The results of real-time PCR were consistent with those of miRNA microarray. The results showed that miR-510, miR-509-5p and miR-508-3p were significantly higher in stage I ovarian cancer than in stage III serous carcinoma. MiR-483 was significantly expressed in stage I Less than Ⅲ serous ovarian cancer. However, the expression of four miRNAs was not associated with other clinicopathological parameters. Survival analysis showed that both miR-510 and miR-509-5p were associated with prognosis, and the prognosis of high expression group was significantly better than that of low expression group. Conclusions MiRNAs are involved in the development of ovarian serous carcinoma. MiR-510 and miR-509-5p may play a role in the invasion and metastasis of ovarian cancer, which is expected to become a molecular marker for predicting the prognosis of ovarian cancer.