共表达网络中lnc-RAPGEF2-3:1在甲状旁腺肿瘤诊断中的价值研究

Diagnostic value of lnc-RAPGEF2-3:1 from the lncRNA-mRNA co-expression network in patients with parathyroid tumor

目的 探讨甲状旁腺腺瘤(PA)中关键lncRNA在PA与甲状旁腺癌(PC)鉴别诊断中的价值。方法 选择2017-01-01-2021-02-28在北京世纪坛医院手术治疗的原发性甲状旁腺功能亢进症患者57例,其中PA 46例,PC 11例。在PA中构建差异lncRNA与mRNA的共表达网络,在该网络中选择与之有关的mRNA数目最多的关键lncRNA,且满足芯片中均一化信号值>7的lnc-RAPGEF2-3:1。通过实时荧光定量聚合酶链反应(qRT-PCR)试验验证PA及PC标本中lnc-RAPGEF2-3:1的表达,分析lnc-RAPGEF2-3:1与患者临床特征的相关性,并使用受试者工作特征(ROC)曲线评估其在PA与PC鉴别诊断中的价值。结果 在PA组中构建共表达网络,与lnc-RAPGEF2-3:1存在相关性的mRNA最多(共9条),其中双功能凋亡调节因子(r_(s)=0.982,P<0.001)及脂肪酸结合蛋白5(r_(s)=0.996,P<0.001)与lnc-RAPGEF2-3:1呈正相关,寡核苷酸结合摺叠区1基因(r_(s)=-0.997,P<0.001)和抗肌萎缩蛋白(r_(s)=-0.997,P<0.001)与其呈负相关。PC组与PA组lnc-RAPGEF2-3:1的表达分别为-4.470(-6.270,-0.090)和-5.885(-6.645,-5.317),差异有统计学意义,Z=-2.022,P=0.043。lnc-RAPGEF2-3:1在PA组中与甲状旁腺素(PTH)、血钙及肿瘤大小均无关联,是PA的保护因素(OR=0.485,95%CI:0.273~0.859,P=0.013)。在PA与PC的鉴别诊断中,lnc-RAPGEF2-3:1联合临床指标(血钙、PTH及肿瘤大小)的ROC曲线下面积达0.800(95%CI:0.673~0.895,P<0.001),与本课题组前期关注的“lncRNA score”差异无统计学意义,Z=1.008,P=0.314。结论 lnc-RAPGEF2-3:1可能是PA患者的lncRNA-mRNA共表达网络中重要的调控点,与临床指标联合后可能为PA与PC的鉴别诊断提供新的方法。

Objective To access the value of key lncRNA from the lncRNA-mRNA co-expression network in parathyroid tumor diagnosis.Methods Fifty-seven patients with primary hyperparathyroidism were involved in this study.They underwent operations in Beijing Shijitan Hospital from January 1,2017 to February 28,2021.There were 46 patients diagnosed with parathyroid adenoma(PA) and 11 patients confirmed with parathyroid carcinoma(PC).The lncRNA-mRNA co-expression network was conducted among patients with PA.Particularly,lnc-RAPGEF2-3:1,which was associated with the most mRNAs,was detected using quantitative real-time polymerase chain reaction(qRT-PCR).Associations between lnc-RAPGEF2-3:1 and clinical characteristics were also analyzed in PA patients.Furthermore,a receiver operating characteristic(ROC) curve was used to assess its role in the differential diagnosis of PA.Results In the lncRNA-mRNA co-expression network for PA,9 mRNAs were associated with lnc-RAPGEF2-3:1.BFAR(r_(s)=0.982,P<0.001) and FABP5(r_(s)=0.996,P<0.001) were positively linked with lnc-RAPGEF2-3:1,whereas OBFC1(r_(s)=-0.997,P<0.001),UTRN(r_(s)=-0.997,P<0.001) were negatively linked with it.Compared with PC,expression level of lnc-RAPGEF2-3:1 was significantly lower in PA,-4.470(-6.270,-0.090) vs-5.885(-6.645,-5.317),Z=-2.022,P=0.043.Moreover,lnc-RAPGEF2-3:1 was a protective factor for PA,which was independent of serum calcium,parathyroid hormone(PTH)and tumor size(OR=0.485,95%CI:0.273-0.859,P=0.013).In the differential diagnosis of PA from PC,the area under the curve(AUC)for the combination of lnc-RAPGEF2-3:1and the clinical index(AUC=0.800,95%CI:0.673-0.895,P<0.001)did not significantly differ from the lncRNA score in the previous study(Z=1.008,P=0.314).Conclusions Lnc-RAPGEF2-3:1may play a vital role in the lncRNA-mRNA co-expression network for patients with PA.The combination of lnc-RAPGEF2-3:1and the clinical index may provide a novel way in the differential diagnosis between PA and PC.