长链非编码RNA PCGEM1、microRNA-642a-5p表达与HPV阳性宫颈癌根治术术后复发的关系研究

Relationship of expression of LncRNA PCGEM1 and microRNA-642a-5p with recurrence of HPV-positive cervical cancer after radical resection

摘要:

目的 探讨长链非编码RNA PCGEM1（LncRNA PCGEM1）、microRNA-642a-5p（miR-642a-5p）表达与人乳头状瘤病毒（HPV）阳性宫颈癌根治术术后复发的关系。方法 选取2018年2月—2020年4月淄博市妇幼保健院184例HPV阳性宫颈癌患者为研究对象，所有患者行HPV阳性宫颈癌根治术。比较不同临床分期HPV阳性宫颈癌LncRNA PCGEM1、miR-642a-5p的表达。统计HPV阳性宫颈癌患者术后2年复发情况，并依据术后是否复发分为复发组和未复发组，比较复发组与未复发组患者的临床资料。多因素Logistic逐步回归分析影响HPV阳性宫颈癌患者术后复发的因素。绘制受试者工作特征（ROC）曲线，以ROC曲线下面积（AUC）评价宫颈癌组织LncRNA PCGEM1、miR-642a-5p表达及两者联合对HPV阳性宫颈癌患者术后复发的预测价值。结果 临床分期Ⅲ期和Ⅱ期宫颈癌组织LncRNA PCGEM1 mRNA相对表达量高于Ⅰ期（P <0.05），miR-642a-5p mRNA相对表达量低于Ⅰ期（P <0.05）；临床分期Ⅲ期宫颈癌组织LncRNA PCGEM1 mRNA相对表达量高于Ⅱ期（P <0.05），miR-642a-5p mRNA相对表达量低于Ⅱ期（P <0.05）。HPV阳性宫颈癌患者术后复发率为15.22%。复发组与未复发组临床分期、分化程度、宫颈浸润深度、盆腔淋巴结转移、肿瘤最大直径比较，差异有统计学意义（P <0.05），复发组宫颈癌组织LncRNA PCGEM1 mRNA相对表达量高于未复发组（P <0.05），miR-642a-5p mRNA相对表达量低于未复发组（P <0.05）。多因素Logistic逐步回归分析显示，临床分期为Ⅲ期［O^R=2.815（95% CI：1.226，6.462）、盆腔淋巴结转移［O^R=2.892（95% CI：1.202，6.968）、宫颈癌组织LncRNA PCGEM1表达［O^R=3.267（95% CI：1.642，8.754）、miR-642a-5p表达［O^R=3.337（95% CI：2.031，9.846）为影响HPV阳性宫颈癌患者术后复发的危险因素（P <0.05）。ROC曲线分析结果显示，宫颈癌组织LncRNA PCGEM1、miR-642a-5p及两者联合预测HPV阳性宫颈癌患者术后复发的敏感性分别为75.00%（95% CI：0.548，0.886）、78.57%（95% CI：0.586，0.910）和75.00%（95% CI：0.548，0.886），特异性分别为78.21%（95% CI：0.708，0.842）、73.08%（95% CI：0.653，0.797）和96.15%（95% CI：0.914，0.984），AUC分别为0.724（95% CI：0.653，0.787）、0.796（95% CI：0.730，0.851）和0.856（95% CI：0.797，0.904）。结论 宫颈癌组织LncRNA PCGEM1、miR-642a-5p与HPV阳性宫颈癌根治术术后复发相关，且两者联合对宫颈癌根治术术后复发的预测效能较高。

Abstract:

Objective To investigate the relationship of the expression of long non-coding ribonucleic acid (LncRNA) prostate cancer gene expression marker 1 (PCGEM1) and microRNA-642a-5p (miR-642a-5p) with human papillomavirus (HPV) positive cervical cancer relationship to postoperative recurrence.Methods A total of 184 patients with HPV-positive cervical cancer who underwent radical surgery for HPV-positive cervical cancer in our hospital from February 2018 to April 2020 were selected. The expression levels of LncRNA PCGEM1 and miR-642a-5p in HPV-positive cervical cancer patients with different clinical stages were compared. The postoperative recurrence of HPV-positive cervical cancer patients was counted 2 years after surgery, and was divided into a recurrence group (28 cases) and a non-recurrence group (156 cases) according to whether or not there was recurrence after surgery. The clinical data of the patients in the recurrence group and the non-relapse group were compared. Logistic multivariate regression analysis of factors influencing postoperative recurrence in patients with HPV-positive cervical cancer. The receiver operating characteristic curve (ROC) was prepared, and the area under the curve (AUC) was used to evaluate the predictive value of LncRNA PCGEM1, miR-642a-5p, and their combination in cervical cancer tissue for postoperative recurrence of HPV-positive cervical cancer patients.Results The levels of LncRNA PCGEM1 in cervical cancer tissues of patients with stage Ⅲ and stageⅡ were higher than those in patients with stage I (P < 0.05), and miR-642a-5p was lower than that in patients with stage I (P < 0.05). The level of LncRNA PCGEM1 in cervical cancer tissue of stage Ⅲ patients was higher than that of stage Ⅱ patients (P < 0.05), and the miR-642a-5p was lower than that of stage Ⅱ patients (P < 0.05). The postoperative recurrence rate of HPV-positive cervical cancer patients was 15.22%. In the recurrence group, the proportion of clinical stage Ⅲ/Ⅳ, the proportion of poorly differentiated, the proportion of cervical infiltration depth ≥ 1/2, the proportion of pelvic lymph node metastasis, proportion of tumors with a maximum diameter of ≥ 4 cm, the proportion of cervical cancer tissue LncRNA PCGEM1 The expression level was higher than that in the non-recurrence group (P < 0.05), and the expression level of miR-642a-5p was lower than that in the non-relapse group (P < 0.05). Logistic regression results showed that the clinical stages were stage Ⅲ/Ⅳ [O^R = 2.815, (95% CI: 1.226, 6.462) ], pelvic lymph node metastasis [O^R = 2.892, (95% CI: 1.202, 6.968) ], LncRNA PCGEM1 [O^R = 3.267, (95% CI: 1.642, 8.754) ], and miR-642a-5p [O^R = 3.337, (95% CI: 2.031, 9.846) ] in cervical cancer were risk factors for postoperative recurrence in patients with HPV-positive cervical cancer (P < 0.05). The ROC curve analysis results showed that the sensitivity of cervical cancer tissue LncRNA PCGEM1, miR-642a-5p, and their combination in predicting postoperative recurrence of HPV-positive cervical cancer patients was 75.00% (95% CI: 0.548, 0.886), 78.57% (95% CI: 0.585, 0.910), and 75.00% (95% CI: 0.548, 0.886), specificities were 78.21% (95% CI: 0.708, 0.842), 73.08% (95% CI: 0.653, 0.797), and 96.15% (95% CI: 0.914, 0.984), and AUC were 0.724 (95% CI: 0.653, 0.787), 0.796 (95% CI: 0.730, 0.851), and 0.856 (95% CI: 0.797, 0.904).Conclusions LncRNA PCGEM1 and miR-642a-5p in cervical cancer tissue are associated with recurrence after radical resection of HPV-positive cervical cancer, and the combination of the two has high predictive performance for recurrence after radical resection of cervical cancer.