Abstract:Objective: To analyze the expression of keratin 17 (KRT17) and autophagy-related protein-12 (ATG12) in cervical local tissues of patients with low-risk and high-risk human papillomavirus (HPV) infection, and their impact on disease progression. Methods: A total of 203 patients with cervical low-grade squamous intraepithelial lesion (LSIL) from December 2020 to December 2022 were enrolled, including 83 cases of low-risk HPV infection and 120 cases of high-risk HPV infection. All cases were followed up for 2 years and divided into progression group and non-progression group according to the progression of the disease within 2 years. Cervical brush specimens were collected at the initial diagnosis, and the expression levels of KRT17 mRNA and ATG12 mRNA were detected by quantitative real-time fluorescence PCR. The levels of KRT17 mRNA and ATG12 mRNA between patients with low-risk and high-risk HPV infection were compared. Point-biserial correlation analysis was used to analyze the correlation between the levels of KRT17 mRNA and ATG12 mRNA and the type of HPV infection. The clinical data, KRT17 mRNA, and ATG12 mRNA levels were compared between the progression group and the non-progression group. Multivariate unconditional Logistic regression analysis was used to analyze the influencing factors of disease progression in patients with LSIL under different HPV status. Logistic (OR) analysis was used to investigate whether there was an additive interaction between KRT17 mRNA and ATG12 mRNA in the progression of LSIL in patients with high-risk HPV infection, and to determine the statistical type of interaction. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of KRT17 mRNA, ATG12 mRNA, and their combination in predicting the progression of LSIL. Results: The expression level of KRT17 mRNA in the high-risk HPV infection group was significantly higher than that in the low-risk HPV infection group (1.35±0.42 vs 0.61±0.20, t=-20.666, P<0.001), while the expression level of ATG12 mRNA was significantly decreased (0.48±0.12 vs 0.80±0.24, t=11.911, P<0.001). Point-biserial correlation analysis showed that KRT17 mRNA was positively correlated with the type of HPV infection (r=0.862, P<0.001). ATG12 mRNA was negatively correlated with HPV infection type (r=-0.799, P<0.001). The proportion of patients with more than one sexual partner, the proportion of patients taking contraceptives frequently, the proportion of patients with high-risk HPV infection, KRT17 mRNA and ATG12 mRNA in the progression group were 15.38%, 23.08%, 97.44%, (1.35±0.30) and (0.33±0.11), respectively, compared with those in the non-progression group 3.05%, 4.27%, 27.44%, (0.98±0.31), (0.68±0.22), the differences were statistically significant (t/χ2= 9.580, 12.870, 61.008, 6.740, -9.640, P= 0.008, <0.001, <0.001, <0.001, <0.001). Multivariate unconditional Logistic regression analysis showed that after adjusting for the number of sexual partners and regular use of contraceptives, KRT17 mRNA and ATG12 mRNA were independent influencing factors for the progression of LSIL in all patients. With each 1 unit increase in these two factors, the risk of progression of LSILwas increased by 1.404 and 0.517 times, respectively (P<0.05). After stratification according to HPV infection type, KRT17 mRNA and ATG12 mRNA were still independent influencing factors for the progression of LSIL in patients with high-risk HPV infection (P<0.05), but in patients with low-risk HPV infection, KRT17 mRNA and ATG12 mRNA were not correlated with the progression of LSIL(P>0.05). The interaction analysis showed that after correcting for the number of sexual partners and regular use of contraceptives, S=1.874, RERI=1.594, and AP=0.361, suggesting that KRT17 mRNA and ATG12 mRNA had a statistically additive synergistic interaction on the progression of the disease; ROC analysis showed that the combined AUC was significantly greater than that of KRT17 mRNA and ATG12 mRNA alone (P<0.05). Conclusion: High expression of KRT17 and low expression of ATG12 synergistically promote the progression of LSIL in patients with high-risk HPV infection. Combined detection of KRT17 and ATG12 can be used as an effective risk warning tool, providing a new basis for precise management and intervention of LSIL.
郭艳蒲, 牛会坤, 许静. 低危与高危型HPV感染患者宫颈KRT17和ATG12的表达及对病情进展的影响[J]. 河北医学, 2026, 32(1): 137-144.
GUO Yanpu, et al. Expression of Cervical KRT17 and ATG12 in Patients with Low-risk and High-risk HPV Infection and Their Influence on Disease Progression. HeBei Med, 2026, 32(1): 137-144.
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