宫颈局部miR-135a-5p、FAK mRNA表达与宫颈癌前病变环形电切术后高危人乳头瘤病毒再活化的相关性

Correlations of expression of miR-135a-5p and FAK mRNA in the partial cervix with high-risk human papillomavirus reactivation after loop electrosurgical excision procedure for cervical precancerous lesions

  • 摘要:
    目的 探讨宫颈局部微小核糖核酸-135a-5p(miR-135a-5p)、黏着斑激酶(FAK) mRNA表达与宫颈癌前病变环形电切术(LEEP)后高危人乳头瘤病毒(HPV)再活化的相关性。
    方法 选取2020年1月—2023年7月延安大学附属医院收治的225例拟行LEEP的宫颈癌前病变患者为研究对象, 对其中203例术后高危HPV转阴患者随访1年(随访期间1例失访),根据高危HPV再活化情况分为再活化组20例、非再活化组182例。比较2组基线资料以及宫颈局部miR-135a-5p、FAK mRNA表达水平; 采用平滑拟合曲线和限制性立方样条(RCS)曲线分析宫颈局部miR-135a-5p、FAK mRNA表达与术后高危HPV再活化的相关性; 采用COX回归方程分析术后高危HPV再活化的影响因素; 采用受试者工作特征(ROC)曲线分析miR-135a-5p、FAK mRNA表达的预测价值。
    结果 再活化组多重感染患者比率以及miR-135a-5p、FAK mRNA表达水平高于非再活化组,差异有统计学意义(P < 0.05)。绘制平滑拟合曲线显示,宫颈局部miR-135a-5p、FAK mRNA表达与术后高危HPV再活化呈现非线性相关性(P趋势 < 0.05, P非线性 < 0.05)。绘制RCS曲线显示,当miR-135a-5p < 1.35时,术后高危HPV再活化风险无显著波动; 当miR-135a-5p≥1.35时,术后高危HPV再活化风险显著增加(P趋势 < 0.05, P非线性 < 0.05); 当FAK mRNA < 1.20时,术后高危HPV再活化风险无显著波动; 当FAK mRNA≥1.20时,术后高危HPV再活化风险显著增加(P趋势 < 0.05, P非线性 < 0.05)。COX回归分析结果显示,校正多重感染后,宫颈局部miR-135a-5p≥1.35、FAK mRNA≥1.20仍是术后高危HPV再活化的影响因素(P < 0.05)。ROC曲线显示, miR-135a-5p、FAK mRNA联合预测的曲线下面积(AUC)值为0.869(95% CI: 0.814~0.912), 大于miR-135a-5p单独预测的AUC值0.734(95% CI: 0.668~0.794)、FAK mRNA单独预测的AUC值0.723(95% CI: 0.656~0.784), 差异均有统计学意义(P < 0.05)。
    结论 宫颈局部miR-135a-5p、FAK mRNA表达与宫颈癌前病变LEEP术后高危HPV再活化相关。当miR-135a-5p≥1.35、FAK mRNA≥1.20时,高危HPV再活化风险显著升高, 2项指标联合检测或有助于早期识别高危HPV再活化高危群体。

     

    Abstract:
    Objective To investigate the correlations of expressions of microRNA-135a-5p (miR-135a-5p) and focal adhesion kinase (FAK) mRNA in the partial cervix with high-risk human papillomavirus (HPV) reactivation after loop electrosurgical excision procedure (LEEP) for cervical precancerous lesions.
    Methods A total of 225 patients with cervical precancerous lesions scheduled for LEEP in the Affiliated Hospital of Yan'an University from January 2020 to July 2023 were selected as the study subjects. Among them, 203 patients who turned negative for high-risk HPV after surgery were followed up for 1 year (1 patient was lost during follow-up during). Based on the reactivation status of high-risk HPV, they were divided into reactivation group (n=20) and non-reactivation group (n=182). Baseline data and expression levels of miR-135a-5p and FAK mRNA in the partial cervix were compared between the two groups. Smooth fitting curves and restricted cubic spline (RCS) were used to analyze the correlation of expression of miR-135a-5p and FAK mRNA in the partial cervix with postoperative high-risk HPV reactivation. Cox regression equations were employed to analyze the influencing factors of postoperative high-risk HPV reactivation. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of the expression of miR-135a-5p and FAK mRNA.
    Results The proportion of patients with multiple infections and the expression levels of miR-135a-5p and FAK mRNA were significantly higher in the reactivation group than that in the non-reactivation group (P < 0.05). The smooth fitting curves showed non-linear correlations of expression of miR-135a-5p and FAK mRNA in the partial cervix with postoperative high-risk HPV reactivation (Ptrend < 0.05, Pnon-linearity < 0.05). The RCS curves revealed that when miR-135a-5p < 1.35, there was no significant fluctuation in the risk of postoperative high-risk HPV reactivation; when miR-135a-5p ≥ 1.35, the risk of postoperative high-risk HPV reactivation significantly increased (Ptrend < 0.05, Pnon-linearity < 0.05). When FAK mRNA < 1.20, there was no significant fluctuation in the risk of postoperative high-risk HPV reactivation; when FAK mRNA ≥ 1.20, the risk of postoperative high-risk HPV reactivation significantly increased (Ptrend < 0.05, Pnon-linearity < 0.05). Cox regression analysis showed that after adjusting for multiple infections, miR-135a-5p ≥ 1.35 and FAK mRNA≥1.20 in the partial cervix remained influencing factors for postoperative high-risk HPV reactivation (P < 0.05). The ROC curves demonstrated that the area under the curve(AUC) value for the combined prediction of miR-135a-5p and FAK mRNA was 0.869 95% confidence interval (CI), 0.814 to 0.912, which was significantly greater than the 0.734(95% CI, 0.668 to 0.794) for the prediction by miR-135a-5p alone and the 0.723 (95% CI, 0.656 to 0.784) for the prediction by FAK mRNA alone (P < 0.05).
    Conclusion The expression of miR-135a-5p and FAK mRNA in the partial cervixis correlated with high-risk HPV reactivation after LEEP for cervical precancerous lesions. When miR-135a-5p ≥ 1.35 and FAK mRNA ≥ 1.20, the risk of high-risk HPV reactivation significantly increases. The combined detection of these two indicators may help in the early identification of high-risk groups for high-risk HPV reactivation.

     

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