宫颈鳞状细胞癌组织LncRNA XIST、miR-16-5p表达与放疗敏感性和预后的关系

Relationships of expressions of LncRNA XIST and miR-16-5p in cervical squamous cell carcinoma tissues with radiotherapy sensitivity and prognosis

摘要

目的 探讨宫颈鳞状细胞癌(CSCC)组织长链非编码核糖核酸X失活特异性转录本(LncRNA XIST)、微小核糖核酸-16-5p(miR-16-5p)表达与放疗敏感性和预后的关系。方法 选取2019年1月至2021年4月在保定市第一中心医院行放射治疗的CSCC患者的活检癌组织128例,另选取同期在保定市第一中心医院经病理诊断为正常的宫颈组织128例为对照,CSCC患者根据放疗疗效分为抵抗组(42例)和敏感组(86例).采用实时荧光定量聚合酶链式反应检测CSCC活检组织及正常宫颈组织LncRNA XIST、miR-16-5p表达.在线数据库预测LncRNA XIST与miR-16-5p的结合位点,采用皮尔逊法分析LncRNA XIST与miR-16-5p表达的相关性,多因素非条件Logistic回归分析LncRNA XIST、miR-16-5p表达与放疗敏感性的关系,受试者工作特征(ROC)曲线确定LncRNA XIST、miR-16-5p表达对CSCC患者放疗敏感性的预测效能;根据LncRNA XIST、miR-16-5p表达的均值分为高/低表达组,Kaplan-Meier法绘制和比较各组生存曲线。结果 CSCC组织LncRNA XIST表达高于正常宫颈组织(t=22.440,P<0.05),miR-16-5p低于正常宫颈组织(t=18.247,P<0.05).LncRNA XIST与miR-16-5p存在结合位点,LncRNA XIST与miR-16-5p在CSCC组织表达呈负相关(r=-0.722,P<0.05).128例CSCC患者放疗敏感率为67.19%(86/128).低分化、LncRNA XIST高表达为CSCC患者放疗敏感性的独立危险因素(OR=4.725、1.910,P<0.05),miR-16-5p高表达为独立保护因素(OR=0.771,P<0.05).LncRNA XIST、miR-16-5p表达联合预测CSCC患者放疗敏感性的曲线下面积为0.870,大于LncRNA XIST、miR-16-5p表达单独预测的0.794、0.783(Z=2.439、2.872,P=0.015、0.004).128例CSCC患者3年总生存率为82.81%(106/128).LncRNA XIST高表达患者3年总生存率低于LncRNA XIST低表达患者(χ²=8.532,P<0.05),miR-16-5p高表达患者3年总生存率高于miR-16-5p低表达患者(χ²=9.609,P<0.05)。结论 CSCC组织LncRNA XIST呈高表达,miR-16-5p呈低表达,与放疗敏感性和预后不良密切相关,LncRNA XIST、miR-16-5p可能成为CSCC放疗敏感性和预后评估的标志物.

Abstract

Objective To investigate relationships of expressions of long non-coding ribonucleic acid X-inactive specific transcript (LncRNA XIST) and microribonucleic acid-16-5p (miR-16-5p) in cervical squamous cell carcinoma (CSCC) tissues with radiotherapy sensitivity and prognosis of the patients. Methods 128 cases of biopsied cancer tissues from CSCC patients who underwent radiotherapy in our hospital from January 2019 to April 2021 were selected, and another 128 cases of normal cervical tissues diagnosed pathologically in our hospital during the same period were selected as controls. The CSCC patients were divided into resistance group (42 cases) and sensitivity group (86 cases) according to efficacy of radiotherapy. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was employed to detect expression of LncRNA XIST and miR-16-5p in the biopsied CSCC tissues and the normal cervical tissues. The binding site of LncRNA XIST and miR-16-5p was predicted by online database. Pearson correlation analysis was used to analyse correlation between expressions of LncRNA XIST and miR-16-5p. Multifactorial unconditional Logistic regression analysis was used to analyze relationships of expressions of LncRNA XIST and miR-16-5p with sensitivity to radiotherapy. Receiver operating characteristic (ROC) curve was used to analyze predictive efficacy of expressions of LncRNA XIST and miR-16-5p for radiotherapy sensitivity in CSCC patients. The patients were categorized into high/low expression groups according to mean values of LncRNA XIST and miR-16-5p expressions. Kaplan-Meier method was used to plot survival curves in the different groups and compare the surivial curves among the different groups. Results LncRNA XIST expression in the CSCC tissues was higher than that in the normal cervical tissues (t=22.440, P<0.05), while the expression of miR-16-5p in the CSCC tissues was lower than that in the normal cervical tissues (t=18.247, P<0.05). There was a binding site between LncRNA XIST and miR-16-5p, and the expression of LncRNA XIST in the CSCC tissues was negatively correlated with the expression of miR-16-5p in the CSCC tissues (r=-0.722, P<0.05). The radiosensitivity rate in 128 CSCC patients was 67.19% (86/128). Low differentiation of the CSCC tissues and high expression of LncRNA XIST (≥1.28) were independent risk factors for radiotherapy sensitivity in CSCC patients, while high expression of miR-16-5p (≥0.82) was independent protective factor (OR=0.771, P<0.05). The area under the curve (AUC) of combination of expressions of LncRNA XIST and miR-16-5p for predicting radiotherapy sensitivity of the CSCC patients was 0.870, which was greater than 0.794 and 0.783 predicted by single LncRNA XIST expression and single miR-16-5p expression alone (for LncRNA XIST expression: Z=2.439, P=0.015; for miR-16-5p expression: Z=2.872, P=0.004). The 3-year overall survival rate in 128 CSCC patients was 82.81% (106/128). Kaplan-Meier survival curve analysis shown that the 3-year overall survival rate in these patients with high LncRNA XIST expression was lower than that in those patients with low LncRNA XIST expression (Log-rank χ²=8.532, P<0.05), and the 3-year overall survival rate in these patients with high miR-16-5p expression was higher than that in those patients with low miR-16-5p expression (Log-rank χ²=9.609, P<0.05). Conclusion LncRNA XIST highly expresses in the CSCC tissues and miR-16-5p lowly expresses in the CSCC tissues, which are closely related to poor radiotherapy sensitivity and poor prognosis. Therefor, the expressions of LncRNA XIST and miR-16-5p may be markers for radiotherapy sensitivity and prognosis evaluation of the CSCC patients.

关键词

宫颈鳞状细胞癌 / 长链非编码核糖核酸X失活特异性转录本 / 微小核糖核酸-16-5p / 放疗敏感性 / 预后

Key words

cervical squamous cell carcinoma / long non-coding ribonucleic acid X-inactive specific transcript / microribonucleic acid-16-5p / radiotherapy sensitivity / prognosis

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基金资助

河北省医学科学研究课题计划(20220291)