Pan Z M, Tan F C, Chen C X, Zhang W, Li L
Department of Gynecology and Oncology, Affiliated Tumor Hospital of Guangxi Medical University and Key Laboratory of Early Prevention and Treatment of Regional High-incidence Tumors, Ministry of Education, Nanning 530021, China.
Zhonghua Fu Chan Ke Za Zhi. 2021 Feb 25;56(2):121-130. doi: 10.3760/cma.j.cn112141-20200718-00587.
To explore the possible biological function of long-chain non-coding RNA (lncRNA) on epithelial ovarian cancer (EOC) drug resistance and the value of new diagnostic markers through bioinformatics analysis, clinical testing and verification methods. (1) Mining the lncRNA related to EOC and constructing the competing endogenous RNA (ceRNA) regulatory network: comprehensively apply text mining, data prediction and network construction and other bioinformatics methods to establish a potential ceRNA regulatory network related to EOC drug resistance, namely lncRNA-microRNA (miRNA)-mRNA regulatory network. (2) Clinical verification: a total of 95 cancer tissue specimens were collected from EOC patients who underwent cytoreductive surgery at the Affiliated Tumor Hospital of Guangxi Medical University from June 2008 to October 2016, of which 54 were platinum-resistant patients (resistance group), 41 platinum-based drug-sensitive patients (sensitive group). Real-time fluorescent quantitative PCR was used to detect the expression of lncRNA in EOC tissues of the two groups, the effect of lncRNA expression on the prognosis of EOC patients, and the diagnostic efficacy of lncRNA expression on resistance to EOC were also analyzed. (1) Text mining preliminarily screened out 25 differentially expressed lncRNA related to the occurrence and development of EOC, and further subcellular localization analysis found that 8 lncRNA exist in the cytoplasm. Through further data mining, collinear literature analysis and construction of ceRNA, the regulatory network predicts that the two lncRNA molecules, GAS5 and HOTAIR, could serve as key ceRNA molecules. (2) Through real-time fluoressent quantitative PCR verification, it was found that both GAS5 and HOTAIR were highly expressed in drug-resistant EOC tissues, which affects the progression-free survival (PFS) and overall survival (OS) time of patients with drug-resistant EOC independent risk factors (<0.05). The receiver operating characteristic (ROC) area under the curve (AUC) of GAS5 alone was 0.678, the AUC of HOTAIR alone was 0.863, and the AUC of GAS5 combined with HOTAIR was 0.871, and there were statistically significant differences (all <0.05). The high expression of GAS5 and HOTAIR is closely related to the drug resistance of EOC, which could be used as a potential predictor of response to chemotherapy. At the same time, the combined detection of GAS5 and HOTAIR has a certain diagnostic efficiency for patients with platinum-resistant EOC. This method of using the ceRNA regulatory network to predict key molecules will provide new ideas for the diagnosis and treatment of EOC.
通过生物信息学分析、临床检测及验证方法，探讨长链非编码RNA（lncRNA）对上皮性卵巢癌（EOC）耐药的可能生物学功能及新型诊断标志物的价值。（1）挖掘与EOC相关的lncRNA并构建竞争性内源RNA（ceRNA）调控网络：综合应用文本挖掘、数据预测及网络构建等生物信息学方法，建立与EOC耐药相关的潜在ceRNA调控网络，即lncRNA-微小RNA（miRNA）-信使核糖核酸（mRNA）调控网络。（2）临床验证：收集2008年6月至2016年10月在广西医科大学附属肿瘤医院接受减瘤手术的EOC患者的95份癌组织标本，其中54例为铂耐药患者（耐药组），41例为铂类药物敏感患者（敏感组）。采用实时荧光定量PCR检测两组EOC组织中lncRNA的表达，分析lncRNA表达对EOC患者预后的影响以及lncRNA表达对EOC耐药的诊断效能。（1）文本挖掘初步筛选出25个与EOC发生发展相关的差异表达lncRNA，进一步亚细胞定位分析发现8个lncRNA存在于细胞质中。通过进一步的数据挖掘、共线文献分析及ceRNA构建，调控网络预测GAS5和HOTAIR这两个lncRNA分子可能作为关键ceRNA分子。（2）通过实时荧光定量PCR验证，发现GAS5和HOTAIR在耐药EOC组织中均高表达，它们是影响耐药EOC患者无进展生存期（PFS）和总生存期（OS）的独立危险因素（<0.05）。单独GAS5的受试者工作特征（ROC）曲线下面积（AUC）为0.678，单独HOTAIR的AUC为0.863，GAS5与HOTAIR联合的AUC为0.871，差异均有统计学意义（均<0.05）。GAS5和HOTAIR的高表达与EOC的耐药密切相关，可作为化疗反应的潜在预测指标。同时，GAS5和HOTAIR联合检测对铂耐药EOC患者有一定的诊断效能。这种利用ceRNA调控网络预测关键分子的方法将为EOC的诊断和治疗提供新思路。
