子宫内膜癌组织中长链非编码RNA AWPPH和miR-383-5p表达变化与预后的关系

Relationships of long non-coding RNA AWPPH and miR-383-5p expressions with prognosis in patients with endometrial cancer

目的观察子宫内膜癌组织长链非编码RNA(long non-coding RNA, lncRNA)AWPPH、miR-383-5p表达变化,探讨其与子宫内膜癌患者预后的关系。方法 80例子宫内膜癌患者,均行筋膜外全子宫+双附件切除术,根据术中快速冰冻组织病理结果,对高风险患者行盆腔和腹主动脉旁淋巴结清扫术,晚期患者或早期高危患者术后行放、化疗。取手术切除癌组织及癌旁组织,采用实时荧光定量PCR法检测lncRNA AWPPH、miR-383-5p相对表达量,比较癌组织与癌旁组织及不同临床病理特征子宫内膜癌患者癌组织lncRNA AWPPH和miR-383-5p相对表达量,Pearson相关法分析癌组织lncRNA AWPPH与miR-383-5p表达的相关性。依据癌组织lncRNA AWPPH和miR-383-5p相对表达量均值,将子宫内膜癌患者分为lncRNA AWPPH高表达组(lncRNA AWPPH相对表达量≥1.904)38例和lncRNA AWPPH低表达组(lncRNA AWPPH相对表达量<1.904)42例,miR-383-5p高表达组(miR-383-5p相对表达量≥0.314)41例和miR-383-5p低表达组(miR-383-5p相对表达量<0.314)39例,随访至2020年10月,Kaplan-Meier法分析lncRNA AWPPH高、低表达组和miR-383-5p高、低表达组患者的生存情况,Cox回归分析子宫内膜癌患者预后的影响因素。结果癌组织lncRNA AWPPH相对表达量(1.904±0.261)高于癌旁组织(0.515±0.082)(P<0.05),miR-383-5p相对表达量(0.314±0.053)低于癌旁组织(1.611±0.361)(P<0.05)。癌组织lncRNA AWPPH相对表达量在临床分期Ⅲ-Ⅳ期(2.109±0.294)、有淋巴结转移者(2.142±0.298)分别高于临床分期Ⅰ-Ⅱ期(1.811±0.216)、无淋巴结转移者(1.737±0.250)(P<0.05),miR-383-5p相对表达量在临床分期Ⅲ-Ⅳ期(0.252±0.070)、有淋巴结转移者(0.261±0.077)分别低于临床分期Ⅰ-Ⅱ期(0.342±0.039)、无淋巴结转移者(0.351±0.042)(P<0.05)。癌组织lncRNA AWPPH表达与miR-383-5p表达呈负相关(r=-0.611,P<0.001)。80例患者3年总生存率为77.5%;lncRNA AWPPH高表达组3年总生存率(63.2%)低于lncRNA AWPPH低表达组(90.5%)(P<0.05),miR-383-5p高表达组3年总生存率(94.9%)高于miR-383-5p低表达组(61.0%)(P<0.05)。临床分期Ⅲ-Ⅳ期(HR=1.629,95%CI:1.020-2.589,P=0.036)、有淋巴结转移(HR=2.662,95%CI:1.178-6.012,P=0.017)、癌组织lncRNA AWPPH高表达(HR=2.438,95%CI:1.433-4.560,P=0.001)及miR-383-5p低表达(HR=1.760,95%CI:1.118-2.574,P=0.006)是子宫内膜癌患者预后不良的危险因素。结论临床分期Ⅲ-Ⅳ期、有淋巴结转移的子宫内膜癌患者癌组织lncRNA AWPPH表达增高,miR-383-5p表达降低,二者是子宫内膜癌患者预后不良的危险因素。

Objective To observe the expressions of long non-coding RNA(lncRNA)AWPPH and miR-383-5 p in endometrial cancer tissues and to investigate their relationships with the prognosis.Methods All patients underwent extrafascial hysterectomy.Based on the quick frozen histopathological examination result in operation,pelvic and para aortic lymph node dissection was performed in patients with high-risk endometrial cancer,and postoperative conventional radiotherapy and chemotherapy were performed in those with advanced or early high-risk endometrial cancer.Real-time fluorescence quantitative PCR was used to detect the expressions of lncRNA AWPPH and miR-383-5 p in the resected endometrial cancer tissues and adjacent tissues.The relative expressions of lncRNA AWPPH and miR-383-5 p were compared between endometrial cancer tissues and adjacent tissues,and in endometrial cancer patients with different clinicopathological characteristics.Pearson correlation analysis was used to investigate the correlation between lncRNA AWPPH and miR-383-5 p in endometrial cancer tissues.According to the mean relative expressions of lncRNA AWPPH and miR-383-5 p,80 patients with endometrial cancer were divided into 38 patients with lncRNA AWPPH≥1.904(highly-expressed lncRNA AWPPH group)and 42 patients with lncRNA AWPPH<1.904(lowly-expressed lncRNA AWPPH group),as well as into 41 patients with miR-383-5 p≥0.314(highly-expressed miR-383-5 p group)and 39 patients with miR-383-5 p<0.314(lowly-expressed miR-383-5 p group).The patients were followed-up till October,2020.Kaplan-Meier survival analysis was used to evaluate the survival between highly-and lowly-expressed IncRNA AWPPH groups and between highly-and lowly-expressed miR-383-5 p groups.Cox regression analysis was used to assess the influencing factors of the prognosis of patients with endometrial cancer.Results The relative expression of lncRNA AWPPH was higher and the relative expression of miR-383-5 p was lower in endometrial cancer tissues(1.904±0.261,0.314±0.053)than that in adjacent tissues(0.515±0.082,1.611±0.361)respectively(P<0.05).The relative expressions of lncRNA AWPPH were higher in patients with clincical stageⅢ-Ⅳand lymph node metastasis(2.109±0.294,2.142±0.298)than those in patients with clinical stageⅠ-Ⅱand no lymph node metastasis(1.811±0.216,1.737±0.250)(P<0.05).The relative expressions of miR-383-5 p were lower in patients with clincical stageⅢ-Ⅳand lymph node metastasis(0.252±0.070,0.261±0.077)than those in patients with clincical stageⅠ-Ⅱand no lymph node metastasis(0.342±0.039,0.351±0.042)(P<0.05).The relative expression of lncRNA AWPPH in endometrial cancer tissues was negatively correlated with miR-383-5 p(r=-0.611,P<0.001).The 3-year overall survival rate was 77.5%in 80 patients,was lower in highly-expressed lncRNA AWPPH group(63.2%)than that in lowly-expressed lncRNA AWPPH group(90.5%)(P<0.05),and was higher in highly-expressed miR-383-5 p group(94.9%)than that in lowly-expressed miR-383-5 p group(61.0%)(P<0.05).The tumor clinical stageⅢ-Ⅳ(HR=1.629,95%CI:1.020-2.589,P=0.036),lymph node metastasis(HR=2.662,95%CI:1.178-6.012,P=0.017),highly-expressed lncRNA AWPPH(HR=2.438,95%CI:1.433-4.560,P=0.001),and lowly-expressed miR-383-5 p(HR=1.760,95%CI:1.118-2.574,P=0.006)were the risk factors of poor prognosis of endometrial cancer.Conclusion LncRNA AWPPH is highly expressed and miR-383-5 p is lowly expressed in patients with endometrial cancer stageⅢ-Ⅳand lymph node metastasis,both of which are the risk factors of poor prognosis of patients with endometrial cancer.