| 摘要: |
| ［摘要］ 目的 探讨lncRNA XIST在预警卵巢癌耐药及临床不良预后的应用价值，为其作为肿瘤标志物应用于临床提供理论依据。方法 基于Oncomine数据库卵巢癌表达谱芯片分析卵巢癌组织与正常卵巢组织的lncRNA XIST表达差异。基于GEO和TCGA数据库独立表达谱芯片，应用Kaplan-Meier plotter和ROC plotter分析lncRNA XIST与患者预后的关联性及其在预警化疗药物耐药的价值。应用实时荧光定量聚合酶链式反应（RT-qPCR）法检测lncRNA XIST在卵巢癌亲本细胞HeyA8及SKOV3、紫杉醇耐药细胞HeyA8-R及SKOV3-R和卡铂耐药细胞HeyA8-CBP和SKOV3-CBP中的表达情况。结果 与正常卵巢组织相比，卵巢癌组织lncRNA XIST表达水平显著下调（P<0.05）。与lncRNA XIST高表达组相比，lncRNA XIST低表达组在总生存期（OS）、无进展生存期（PFS）和进展后生存期（PPS）方面的预后更差（P<0.05）。RT-qPCR检测结果显示，与卵巢癌敏感细胞HeyA8及SKOV3相比，lncRNA XIST在紫杉醇耐药细胞HeyA8-R和SKOV3-R及卡铂耐药细胞HeyA8-CBP和SKOV3-CBP中均显著下调（P<0.05)。与敏感组织相比，lncRNA XIST在耐药组织中的表达也显著下调，且其低表达潜在预警卵巢癌耐药（P<0.05）。进一步的ROC plotter分析结果显示，对于所有药物耐药，lncRNA XIST的预警截断值为8 977；对于铂类药物耐药，lncRNA XIST的预警截断值为8 977；对于紫杉醇耐药，lncRNA XIST的预警截断值为8 245；对于铂类药物+紫杉醇耐药，lncRNA XIST的预警截断值为8 245，均具有一定的预警价值（P<0.05）。结论 lncRNA XIST有望作为卵巢癌化疗药物耐药和患者预后的预警标志物，具有临床应用价值。 |
| 关键词: lncRNA XIST 卵巢癌 耐药 不良预后 肿瘤标志物 |
| DOI：10.3969/j.issn.1674-3806.2021.05.17 |
| 分类号:R 737.31 |
| 基金项目:国家自然科学基金项目（编号：81860458）；区域性高发肿瘤早期防治研究教育部重点实验室自主研究项目（编号：GKE-ZZ202017） |
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| The application value of lncRNA XIST in prediction of drug resistance and poor prognosis in ovarian cancer |
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CHEN Cui-lan, YIN Fu-qiang
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Institute of Life Sciences, Guangxi Medical University, Nanning 530021, China
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| Abstract: |
| ［Abstract］ Objective To investigate the application value of lncRNA XIST in prediction of drug resistance and poor clinical prognosis in ovarian cancer, and to provide theoretical basis for its clinical application as a tumor marker. Methods The difference of lncRNA XIST expression between ovarian cancer tissues and normal ovarian tissues was analyzed based on microarrays deposited in Oncomine database. Base on the independent expression profile chip of GEO and TCGA databases,Kaplan-Meier plotter and ROC plotter were used to analyze the association between lncRNA XIST and the patients′ prognoses and its value in prediction of chemotherapy resistance. Real-time quantitative polymerase chain reaction(RT-qPCR) was used to detect the expressions of lncRNA XIST in carboplatin-resistant ovarian cancer cells HeyA8-CBP and SKOV3-CBP, taxol-resistant cells HeyA8-R and SKOV3-R, and their sensitive cells HeyA8 and SKOV3. Results Compared with that in normal ovarian tissues, the expression of lncRNA XIST in ovarian cancer tissues was significantly down-regulated(P<0.05). Compared with the high expression group of lncRNA XIST, the low expression group of lncRNA XIST had worse prognoses in overall survival(OS), progression-free survival(PFS), and post-progression survival(PPS)(P<0.05). The detection results of RT-qPCR showed that lncRNA XIST was significantly down-regulated in carboplatin-resistant ovarian cancer cells HeyA8-CBP and SKOV3-CBP, taxol-resistant cells HeyA8-R and SKOV3-R compared with that in sensitive cells HeyA8 and SKOV3(P<0.05). Meanwhile, the expression of lncRNA XIST was significantly decreased in drug resistant tissues compared with that in sensitive tissues, and low expression of lncRNA in drug resistant tissues might be a potential prediction of drug resistance in ovarian cancer(P<0.05). Further ROC plotter analysis results showed that for the resistance to all drugs, the warning cutoff value of lncRNA XIST was 8 977; for the resistance to platinum drugs, the predicted cutoff value was 8 977; for the resistance to paclitaxel, the predicted cutoff value was 8 245; for the resistance to platinum drugs+paclitaxel, the predicted cutoff value was 8 245, all of which had a certain predicted value(P<0.05). Conclusion lncRNA XIST is expected to be used as a predictive marker for chemotherapeutic drug resistance to ovarian cancer and the patients′ prognoses, and has clinical application value. |
| Key words: lncRNA XIST Ovarian cancer Drug resistance Poor prognosis Tumor markers |
