LncRNA BANCR表达与TSHR甲基化在BRAF^V600E突变的甲状腺乳头状癌中的研究

The Study of LncRNA BANCR Expression and TSHR Methylation in BRAF^V600E Mutated PTC

摘要: 目的：探讨长链非编码RNA BANCR表达及TSHR甲基化与BRAFV600E突变的甲状腺乳头状癌的关系。方法：收集60例BRAFV600E突变的甲状腺乳头状癌(PTC)患者癌组织样本60例和癌旁正常甲状腺组织样本60例(简称癌旁组织)，上述所有PTC患者已采用荧光定量PCR (QPCR)检测分析上述各样本BANCR基因的表达水平，并应用甲基化特异性聚合酶链反应(Methylation-Specific Polymerase chain reac-tion, MSP)法检测上述各样本中TSHR基因启动子甲基化情况，并分析上述癌组织和癌旁组织中各样本基因表达水平和TSHR甲基化情况与BRAFV600E突变的PTC患者的临床病理特征之间的关系。结果：癌组织组：BANCR相对表达量为(1.55 ± 1.62)，高表达率为66.67%，癌旁组织组分别为(0.74 ± 0.63和30%)，癌组织显著高于癌旁组织(P < 0.05)。癌组织中，BANCR高表达与肿瘤的颈部淋巴结转移存在显著相关性(P < 0.05)。癌组织组中TSHR甲基化的发生率为93.3% (56/60)，癌旁组织组中TSHR甲基化的发生率为18.3% (11/60)，TSHR甲基化PTC患者例数显著高于非甲基化PTC患者，差异均具有统计学意义(P均 < 0.01)。癌组织中BANCR的表达水平及TSHR甲基化以及两者联合检测阳性例数均显著高于癌旁组织，差异具有统计学差异(P均 < 0.05)，BANCR高表达联合TSHR甲基化对BRAFV600E突变的PTC诊断的灵敏度、特异性和准确性较单项检测均出现上升趋势，但仅灵敏度与单一检测相比差异具有统计学意义(P < 0.05)。结论：BANCR高表达和TSHR甲基化均与BRAFV600E突变的PTC患者颈部淋巴结转移密切相关，与肿瘤的进展相关并提示不良预后。且BANCR高表达联合TSHR甲基化对BRAFV600E突变的PTC临床诊断具有较佳的灵敏度。

Abstract: Objective: To investigate the relationship between long non-coding RNA BANCR expression and TSHR methylation and BRAFV600E-mutated papillary thyroid carcinoma (PTC). Methods: Collecting 60 cancer tissue samples and 60 adjacent normal thyroid tissue samples (adjacent tissue) from 60 patients with BRAFV600E mutation in PTC, the expression levels of BANCR genes were analyzed for each of the above samples by fluorescence quantitative PCR (QPCR), and applied the methyla-tion-specific polymerase chain reaction (MSP) for promoter methylation of the TSHR gene in these samples, and analyzed the relationship between gene expression levels and TSHR methylation of each sample in both cancerous and adjacent tissues and the clinicopathological characteristics of patients with PTC with BRAFV600E mutations. Results: The cancer tissue group: the relative expression level of BANCR was (1.55 ± 1.62), the high expression rate was 66.67%, and the adjacent tissue group was (0.74 ± 0.63 and 30%, respectively), and the cancer tissue was significantly higher than the adjacent tissue (P < 0.05). There is significant correlation between high BANCR expression and cervical lymph node metastasis in cancer tissues (P < 0.05). The incidence of TSHR methylation was 93.3% (56/60) in the cancer tissue group and 18.3% (11/60) in the paracancer tissue group, the number of TSHR methylated PTC patients was significantly higher than non-methylated PTC patients, and the differences were statistically significant (P < 0.01). The expression level of BANCR, TSHR methylation and the number of positive cases were significantly higher than that of carcinoma tissue and statistically different (P < 0.05). The sensitivity, specificity and accuracy of BANCR high expression combined with TSHR methylation for PTC diagnosis of BRAFV600E mutation showed an increasing trend compared with individual detection, but the sensitivity was statistically different compared with the single test (P < 0.05). Conclusion: High BANCR expression and TSHR methylation are closely related with cervical lymph node metastasis in PTC patients with BRAFV600E mutation, which is associated with tumor progression and indicates poor prognosis. Moreover, high expression of BANCR combined with TSHR methylation has better sensitivity for clinical diagnosis of PTC with BRAFV600E mutation.