血清微小RNA-501、微小RNA-143、细胞周期G1至S期转换蛋白1 mRNA对人乳头状瘤病毒感染宫颈癌放化疗敏感性的预测价值

Predictive value of serum microRNA-501, microRNA-143, and cell cycle G1 to S phase transition protein 1 mRNA for chemoradiation sensitivity in human papillomavirus-infected cervical cancer

  • 摘要:
    目的 探讨血清微小RNA(miR)-501、miR-143、细胞周期G1至S期转换蛋白1(GSPT1)mRNA对人乳头状瘤病毒(HPV)感染宫颈癌患者放化疗敏感性的预测价值。
    方法 选取183例HPV感染宫颈癌患者作为研究对象,检测血清miR-501、GSPT1 mRNA、miR-143表达水平。所有患者接受调强放疗同步紫杉醇、顺铂化疗,依据放化疗敏感性的不同分为不敏感组和敏感组,比较2组一般资料及血清miR-501、GSPT1 mRNA、miR-143表达水平。采用Spearman相关分析法分析各变量间的相关性,采用Logistic回归方程分析HPV感染宫颈癌患者放化疗敏感性的影响因素,通过受试者工作特征(ROC)曲线及曲线下面积(AUC)、Hosmer-Lemeshow拟合优度检验评估miR-501、GSPT1 mRNA、miR-143单独及联合预测HPV感染宫颈癌患者放化疗敏感性的价值,并对联合预测效能进行外部验证。
    结果 不敏感组患者的肿瘤直径、肿瘤分期、分化程度、淋巴结转移情况、HPV分型与敏感组比较,差异有统计学意义(P < 0.05); 不敏感组miR-501、GSPT1 mRNA相对表达量高于敏感组, miR-143相对表达量低于敏感组,差异有统计学意义(P < 0.05)。肿瘤直径、肿瘤分期、淋巴结转移、HPV分型均分别与miR-501、GSPT1 mRNA呈正相关,与miR-143呈负相关(P < 0.05); 分化程度分别与miR-501、GSPT1 mRNA呈负相关,与miR-143呈正相关(P < 0.05)。分化程度、miR-143、HPV分型、GSPT1 mRNA、miR-501均为HPV感染宫颈癌患者放化疗敏感性的独立影响因素(P < 0.05)。ROC曲线显示, miR-501、GSPT1 mRNA、miR-143三者联合预测HPV感染宫颈癌患者放化疗敏感性的价值高于单独预测。Hosmer-Lemeshow拟合优度检验显示, χ2=11.810, P=0.158, 表明模型拟合良好。外部验证显示, 联合预测结果与实际结果的一致性较高, Kappa值为0.754。
    结论 血清miR-143、miR-501、GSPT1 mRNA是HPV感染宫颈癌患者放化疗敏感性的影响因素,三者联合检测对放化疗敏感性具有良好的预测价值,可用于制订针对性治疗方案,促进疾病良好转归。

     

    Abstract:
    Objective To investigate the predictive value of serum microRNA (miR)-501, miR-143, and cell cycle G1 to S phase transition protein 1 (GSPT1) mRNA for chemoradiation sensitivity in patients with human papillomavirus (HPV)-infected cervical cancer.
    Methods A total of 183 patients with HPV-infected cervical cancer were selected as study subjects. The expression levels of serum miR-501, GSPT1 mRNA, and miR-143 were detected. All patients received intensity-modulated radiotherapy combined with paclitaxel and cisplatin chemotherapy. Based on chemoradiation sensitivity, they were divided into non-sensitive group and sensitive group. The general information and the expression levels of serum miR-501, GSPT1 mRNA, and miR-143 were compared between the two groups. Spearman correlation analysis was used to analyze the correlations among variables. Logistic regression analysis was employed to identify the influencing factors of chemoradiation sensitivity in patients with HPV-infected cervical cancer. The value of miR-501, GSPT1 mRNA, and miR-143 separately and jointly predicting chemoradiation sensitivity in patients with HPV-infected cervical cancer was evaluated using the receiver operating characteristic (ROC) curve, the area under the curve (AUC), and the Hosmer-Lemeshow goodness-of-fit test. External validation was conducted to assess predictive efficacy of the combined detection.
    Results There were significant differences in tumor diameter, tumor stage, degree of differentiation, lymph node metastasis, and HPV typing between the non-sensitive group and the sensitive group (P < 0.05). The relative expression levels of miR-501 and GSPT1 mRNA in the non-sensitive group were higher than those in the sensitive group, while the relative expression level of miR-143 in the non-sensitive group was lower than that in the sensitive group, with statistically significant differences (P < 0.05). Tumor diameter, tumor stage, lymph node metastasis, and HPV typing were positively correlated with miR-501 and GSPT1 mRNA, respectively, and negatively correlated with miR-143 (P < 0.05). The degree of differentiation was negatively correlated with miR-501 and GSPT1 mRNA, respectively, and positively correlated with miR-143 (P < 0.05). The degree of differentiation, miR-143, HPV typing, GSPT1 mRNA, and miR-501 were all independent influencing factors for chemoradiation sensitivity in patients with HPV-infected cervical cancer (P < 0.05). The ROC curve showed that the value of the joint prediction of miR-501, GSPT1 mRNA, and miR-143 for chemoradiation sensitivity in patients with HPV-infected cervical cancer was higher than separate prediction. The Hosmer-Lemeshow goodness-of-fit test showed that χ2=11.810 and P=0.158, indicating a good model fit. External validation showed a high consistency between the joint prediction results and the actual results, with a Kappa valueof 0.754.
    Conclusion Serum miR-143, miR-501 and GSPT1 mRNA are influencing factors for chemoradiation sensitivity in patients with HPV-infected cervical cancer. The joint detection of these three markers has a good predictive value for chemoradiation sensitivity and can be used to formulate targeted treatment plans and promote favorable disease outcomes.

     

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