血清LTBP2、CEACAM6与HPV感染交互作用对宫颈癌临床预后的影响

Interaction of serum LTBP2, CEACAM6 and HPV infection on the prognosis of cervical cancer

摘要

目的 探讨血清转化生长因子结合蛋白2(LTBP2)、癌胚抗原相关细胞黏附分子6(CEACAM6)与人乳头瘤病毒(HPV)感染交互作用对宫颈癌临床预后的影响。方法 本研究采用前瞻性研究方法,选取2022年5月至2024年5月河北北方学院附属第一医院收治的242例宫颈癌患者,均采取宫颈癌根治术治疗,以术后1年内复发作为临床预后判定标准,分为复发组和未复发组。统计两组一般资料、血清LTBP2、CEACAM6水平及HPV感染,采用Logistic回归分析宫颈癌临床预后的影响因素,采用相加及相乘模型分析LTBP2、CEACAM6与HPV感染交互作用,绘制受试者工作特征(ROC)曲线获取曲线下面积(AUC),评价LTBP2、CEACAM6与HPV感染对宫颈癌临床预后的预测价值。结果 术后1年,242例宫颈癌患者中3例失访,复发率为16.74%(40/239)。复发组FIGO分期Ⅱ期、肌层浸润深度≥1/2、中低分化程度、高危型HPV感染率及血清LTBP2、CEACAM6水平均高于未复发组(t/χ²=4.766、6.195、6.068、18.338、6.424、6.618,P<0.05)。在模型1和模型2(校正相关指标后)中,高危型HPV感染(OR=2.894、3.882,95%CI:1.252~6.689、1.488~10.127)、LTBP2(OR=1.817、1.551,95%CI:1.289~2.562、1.211~1.986)、CEACAM6(OR=1.784、1.552,95%CI:1.301~2.447、1.203~2.003)均是宫颈癌临床预后的影响因素(P<0.05);LTBP2(RERI=1.02、3.04,95%CI:0.151~2.890、1.122~5.982)、CEACAM6(RERI=1.05、3.27,95%CI:0.181~2.921、1.251~6.120)高值与高危型HPV感染在宫颈癌临床预后中存在相加交互作用(P<0.05)。血清LTBP2、CEACAM6与HPV感染联合预测宫颈癌临床预后的AUC为0.886,明显高于各指标单独预测(Z=3.035、3.007、4.689,P<0.05)。结论 血清LTBP2、CEACAM6高水平与高危型HPV感染对宫颈癌临床预后具有相加交互作用,三者联合预测效能高,有助于指导临床治疗决策,降低复发风险。

Abstract

Objective To investigate the effect of the interaction between serum transforming growth factor binding protein 2 (LTBP2), carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) and human papillomavirus (HPV) infection on the prognosis of cervical cancer. Methods A prospective study was conducted to select 242 patients with cervical cancer admitted to the First Affiliated Hospital of Hebei North University from May 2022 to May 2024. All patients were underwent radical surgery for cervical cancer. The recurrence within 1 year after operation was used as the prognosis criterion, and they were divided into a recurrence group and a non-recurrence group. The general data, serum LTBP2, CEACAM6 levels and HPV infection of the two groups were compared. Logistic regression was used to analyze the influencing factors of prognosis of cervical cancer. Additive and multiplicative models were used to analyze the interaction between LTBP2, CEACAM6 and HPV infection. The receiver operating characteristic (ROC) curve was drawn to obtain the area under the curve (AUC), and the predictive value of LTBP2, CEACAM6 and HPV infection on the prognosis of cervical cancer was evaluated. Results One year after operation, 3 of the 242 patients with cervical cancer were lost to follow-up, and the recurrence rate was 16.74% (40/239). The FIGO stage Ⅱ, depth of myometrial invasion ≥1/2, degree of medium and low differentiation, high-risk HPV infection rate, serum LTBP2 and CEACAM6 levels in the recurrence group were higher than those in the non-recurrence group (t/χ ²=4.766, 6.195, 6.068, 18.338, 6.424 and 6.618, respectively, P<0.05). In Model 1 and Model 2 (after adjustment for relevant covariates), high-risk HPV infection (OR=2.894 and 3.882; 95%CI: 1.252-6.689 and 1.488-10.127), LTBP2 (OR=1.817 and 1.551; 95%CI: 1.289-2.562 and 1.211-1.986), and CEACAM6 (OR=1.784 and 1.552; 95%CI: 1.301-2.447 and 1.203-2.003) were all influencing factors for prognosis of cervical cancer (P<0.05). High levels of LTBP2 (RERI=1.02 and 3.04; 95%CI: 0.151-2.890 and 1.122-5.982) and CEACAM6 (RERI=1.05 and 3.27; 95%CI: 0.181-2.921 and 1.251-6.120) exhibited additive interaction with high-risk HPV infection in the prognosis of cervical cancer (P<0.05). The AUC of the combination of serum LTBP2, CEACAM6, and HPV infection for predicting prognosis of cervical cancer was 0.886, which was significantly higher than that of each single indicator alone (Z=3.035, 3.007 and 4.689, respectively, P<0.05). Conclusion High serum levels of LTBP2 and CEACAM6, together with high-risk HPV infection, exhibit an additive interaction in the prognosis of cervical cancer. The combined prediction efficiency of the three is high, which is helpful to guide clinical treatment decisions and reduce the risk of recurrence.

关键词

宫颈癌 / 人乳头瘤病毒 / 转化生长因子结合蛋白2 / 癌胚抗原相关细胞黏附分子6 / 临床预后

Key words

cervical cancer / human papillomavirus / transforming growth factor binding protein 2 / carcinoembryonic antigen-related cell adhesion molecule 6 / prognosis

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基金资助

河北省2026年度医学科学研究课题(20261680)