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.