血浆miR-663和sHLA-G在甲状腺乳头状癌中的表达水平及其诊断价值

The expression of plasma miR-663 and sHLA-G in papillary thyroid carcinoma and its diagnostic value

目的探讨甲状腺乳头状癌(papillary thyroid carcinoma,PTC)患者血浆microRNA-663(miR-663)和可溶性人类白细胞抗原-G(soluble human leukocyte antigen-G,s HLA-G)的表达水平在PTC中的诊断价值。方法选取68例PTC(甲状腺癌组)、40例甲状腺腺瘤(甲状腺腺瘤组)和30例健康对照者(健康对照组)。采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)测定血浆s HLA-G表达水平,采用定量反转录聚合酶链反应(quantitative reverse transcription polymerase chain reaction,qRT-PCR)检测血浆miR-663水平。结果甲状腺癌组血浆s HLAG水平均高于甲状腺腺瘤组和健康对照组(均P<0.01)。甲状腺癌组血浆miR-663相对表达水平均低于甲状腺腺瘤组和健康对照组(均P<0.01)。PTC患者血浆s HLA-G水平在肿瘤大小、浸润程度、淋巴结转移和TNM分期方面比较,差异均具有统计学意义(均P<0.05)。血浆miR-663水平在浸润程度、淋巴结转移和TNM分期方面比较,差异均具有统计学意义(均P<0.05)。PTC患者血浆miR-663和s HLA-G的受试者工作特征曲线(receiver operating characteristic,ROC)曲线下面积(area under the curve,AUC)分别为0.208(95%CI:0.123~0.293,P=0.048)和0.790(95%CI:0.708~0.873,P<0.01)。当miR-663的截断值为2.76时,敏感度为87.0%,特异度为54.8%,阳性预测值为66.3%,阴性预测值为58.9%。当s HLA-G的截断值为37.3时,敏感度为64.7%,特异度为82.5%,阳性预测值为64.8%,阴性预测值为52.5%。2个指标联合检测的AUC值为0.502(95%CI:0.391~0.612,P=0.013),敏感度为89.3%,特异度为83.8%,阳性预测值为69.0%,阴性预测值为61.6%。结论血浆miR-663和s HLA-G表达水平可作为甲状腺良恶性疾病鉴别诊断的辅助参考指标,与甲状腺癌的侵袭和转移密切相关。

Objective To detect the plasma levels of microRNA-663(miR-663)and soluble human leukocyte antigen-G(s HLA-G)in patients with papillary thyroid carcinoma(PTC),and investigate the diagnostic value in PTC.Methods Sixty-eight cases of PTC(thyroid carcinoma group),forty cases of thyroid adenoma(thyroid adenoma group),and thirty healthy controls(control group)were selected.Enzyme-linked immunosorbent assay(ELISA)was used to detect the plasma levels of s HLA-G.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the relative expression of miR-663.Results The plasma level of s HLA-G in the thyroid carcinoma group was significantly higher than those in the thyroid adenoma group and the control group(both P<0.01).The plasma level of miR-663 in the thyroid carcinoma group was significantly lower than those in the thyroid adenoma group and the control group(both P<0.01).Plasma s HLA-G level was correlated with tumor size,tumor infiltration,lymph node metastasis,and TNM staging(all P<0.05).Plasma miR-663 level was correlated with tumor infiltration,lymph node metastasis,and TNM staging(all P<0.05).The areas under the receiver operation characteristic curve(AUC)of plasma miR-663 and s HLA-G were0.208(95%CI:0.123-0.293,P=0.048)and 0.790(95%CI:0.708-0.873,P<0.01),respectively.When the cut-off value of miR-663 was 2.76,the sensitivity was 87.0%,the specificity was 54.8%,the positive predictive value was 66.3%,and the negative predictive value was 58.9%.When the cut-off value of s HLA-G was 37.3,the sensitivity was 64.7%,the specificity was 82.5%,the positive predictive value was 64.8%,and the negative predictive value was52.5%.The AUC of the combined detection of the two indexes was 0.502(95%CI:0.391-0.612,P=0.013),with a sensitivity of 89.3%,a specificity of 83.8%,a positive predictive value of 69.0%,and a negative predictive value of61.6%.Conclusion The plasma levels of s HLA-G and miR-663 can be used as a supplementary reference for the differential diagnosis of benign and malignant thyroid diseases,which is closely related to the invasion and metastasis of thyroid carcinoma.