Survivin联合CXCL13对宫颈上皮内瘤变病变程度的评估价值

Value of survivin combined with CXCL13 in evaluating the grade of cervical intraepithelial neoplasia

摘要:

目的 探讨Survivin联合CXC亚家族趋化因子配体13（CXCL13）对宫颈上皮内瘤变（CIN）病变程度的评估价值。方法 选取2020年1月—2023年1月淄博市妇幼保健院手术切除的101例CIN组织石蜡标本作为研究组，其中CIN 3级（高级别宫颈病变）组织石蜡标本38例，CIN 2级（高级别宫颈病变）42例，CIN 1级（低级别宫颈病变）21例。另选取同期该院因子宫肌瘤行子宫切除的正常宫颈组织石蜡标本101例作为对照组。采用免疫组织化学染色测定不同宫颈组织标本中Survivin、CXCL13蛋白表达；采用多因素逐步Logistic回归分析CIN病变程度的影响因素；绘制受试者工作特征（ROC）曲线分析Survivin、CXCL13蛋白评估CIN病变程度的诊断效能。结果 CIN 3级宫颈组织Survivin蛋白阳性表达率均高于CIN 1、2级宫颈组织、正常宫颈组织（P <0.05），CXCL13蛋白阳性表达率均低于CIN 1、2级宫颈组织、正常宫颈组织（P <0.05）；CIN 2级宫颈组织Survivin蛋白阳性表达率均高于CIN 1级宫颈组织、正常宫颈组织（P <0.05），CXCL13蛋白阳性表达率均低于CIN 1级宫颈组织、正常宫颈组织（P <0.05）；CIN 1级宫颈组织中Survivin蛋白阳性表达率高于正常宫颈组织（P <0.05），CXCL13蛋白阳性表达率低于正常宫颈组织（P <0.05）。不同级别病变组年龄、体质量指数、受教育年限、性伴侣>1个占比、妊娠次数、流产次数、分娩次数、初孕年龄、盆腔炎病史占比、阴道炎病史占比、收缩压、舒张压、甘油三酯、总胆固醇、血肌酐、尿酸、白细胞计数、血小板计数比较，差异均无统计学意义（P >0.05）。高级别病变组初次性交年龄低于低级别病变组（P <0.05），高级别病变组口服避孕药、高危型HPV感染、P16阳性、Ki-67阳性占比均高于低级别病变组（P <0.05）。多因素逐步Logistic回归分析结果显示，口服避孕药［O^R=3.114（95% CI：1.281，7.569）］、高危型HPV感染［O^R=5.613（95% CI：2.309，13.640）］、Survivin蛋白阳性［O^R=3.435（95% CI：1.413，8.348）］、CXCL13蛋白阳性［O^R=3.347（95% CI：1.377，8.134）］是影响CIN病变程度的因素（P <0.05）。ROC曲线分析结果显示，Survivin、CXCL13及两者联合评估CIN病变程度的敏感性分别为72.50%（95% CI：0.612，0.816）、67.50%（95% CI：0.560，0.773）、81.25%（95% CI：0.707，0.888），特异性分别为71.43%（95% CI：0.477，0.878）、76.19%（95% CI：0.525，0.909）、90.48%（95% CI：0.682，0.983），曲线下面积分别为0.726（95% CI：0.629，0.822）、0.712（95% CI：0.604，0.819）、0.898（95% CI：0.834，0.963）。结论 Survivin、CXCL13 与CIN病变程度有关，随着CIN病变程度升级，Survivin蛋白阳性表达呈上升趋势、CXCL13蛋白阳性表达呈下降趋势，两者联合评估CIN病变程度效能良好，具有一定的临床价值。

Abstract:

Objective To explore the value of survivin combined with CXC chemokine ligand 13 (CXCL13) in evaluating the grade of cervical intraepithelial neoplasia (CIN).Methods The 101 paraffin samples of CIN tissues surgically removed in our hospital from January 2020 to January 2023 were collected and included as the study group, among which 38 paraffin samples were of CIN3 (high-grade cervical lesions), 42 CIN2 (high-grade cervical lesions), and 21 CIN1 (low-grade cervical lesions). Another 101 paraffin specimens of normal cervical tissues from patients undergoing hysterectomy due to uterine fibroids were selected as the control group. The protein expressions of survivin and CXCL13 in different cervical tissue samples were determined by immunohistochemistry. The factors affecting the grade of CIN lesions and the value of survivin and CXCL13 in evaluating the grade of CIN lesions were analyzed.Results The positive expression rate of survivin in CIN3 tissues was higher than that in CIN1/2 and normal cervical tissues (P < 0.05), and the positive expression rate of CXCL13 in CIN3 tissues was lower than that in CIN1/2 and normal cervical tissues (P < 0.05). The positive expression rate of survivin in CIN2 tissues was higher than that in CIN1 and normal cervical tissues (P < 0.05), and the positive expression rate of CXCL13 in CIN2 tissues was lower than that in CIN1 and normal cervical tissues (P < 0.05). The positive expression rate of survivin in CIN1 tissues was higher than that in normal cervical tissues (P < 0.05), and the positive expression rate of CXCL13 in CIN1 tissues was lower than that in normal cervical tissues (P < 0.05). There was no difference in age, body mass index, year of education, proportion of patients with more than one sex partner, gravidity, parity, number of abortions, age at first pregnancy, proportion of patients with a history of pelvic inflammation, proportion of patients with a history of vaginitis, SBP, DBP, levels of TG, TC, serum creatinine and uric acid, WBC count and PLT count among patients with different grades of CIN lesions (P > 0.05). The age at first sexual intercourse in the high-grade lesion group was lower than that in the low-grade lesion group (P < 0.05), and the percentages of oral contraceptive use, high-risk HPV infection, P16 positivity, and Ki-67 positivity in the high-grade lesion group were higher than those in the low-grade lesion group (P < 0.05). Multivariable stepwise Logistic regression analysis showed that oral contraceptive use [O^R = 3.114, (95% CI: 1.281, 7.569) ], high-risk HPV infection [O^R = 5.613, (95% CI: 2.309, 13.640) ], survivin positivity [O^R = 3.435, 95% CI: 1.413, 8.348) ] and CXCL13 positivity [O^R = 3.347, (95% CI: 1.377, 8.134) ] were the factors affecting the grade of CIN lesions (P < 0.05). The receiver operating characteristic (ROC) curve analysis demonstrated that the sensitivities of survivin, CXCL13 and their combination for evaluating the grade of CIN lesions were 72.50% (95% CI: 61.20%, 81.61%), 67.50% (95% CI: 56.00%, 77.30%), and 81.25% (95% CI: 70.65%, 88.79%), with the specificities being 71.43% (95% CI: 47.69%, 87.81%), 76.19% (95% CI: 52.45%, 90.88%), and 90.48% (95% CI: 68.17%, 98.33%), and the AUCs being 0.726 (95% CI: 0.629, 0.822), 0.712 (95% CI: 0.604, 0.819) and 0.898 (95% CI: 0.834, 0.963).Conclusions Survivin and CXCL13 are related to the grade of CIN lesions, and the positive expression rate of survivin increases while that of CXCL13 decreases with the progression of CIN lesions. The combination of survivin and CXCL13 is effective in evaluating the grade of CIN lesions and holds certain clinical value.