细针穿刺标本中葡萄糖转运体1基因检测在诊断甲状腺癌中的价值
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摘要
目的:探讨葡萄糖转运体1(glucose transporter 1,GLUT1)基因检测在术前鉴别甲状腺良恶性结节中的价值。方法:采用RT-q PCR检测112例甲状腺结节(42例良性,70例恶性)和52例结节周边正常甲状腺细针穿刺(fine needle aspiration,FNA)标本中GLUT1 m RNA的表达量,然后采用免疫组织化学方法检测术后病理组织中GLUT1蛋白的表达情况。构建受试者工作特征(re-ceiver operating characteristic,ROC)曲线评价GLUT1基因对甲状腺癌的诊断价值。结果:甲状腺结节FNA标本中可以检测出GLUT1 m RNA的表达,且其与术后免疫组化GLUT1蛋白的表达水平相一致。PCR结果表明GLUT1基因在良性结节与正常甲状腺细胞之间的表达水平无显著性差异(P>0.05)。与良性结节相比,甲状腺癌中GLUT1基因表达水平显著增高(P<0.001)。GLUT1基因诊断甲状腺癌的敏感性、特异性及ROC曲线下面积(AUC)分别为62.9%、92.9%和0.797。甲状腺癌中GLUT1基因表达与年龄、性别、肿瘤大小、结节数目、BRAFV600E突变和淋巴结转移均未见明显相关性(P>0.05),但与AJCC分期显著相关(P<0.001)。结论:GLUT1基因检测对甲状腺癌的诊断具有较高的特异性,可作为术前鉴别甲状腺良恶性病变的重要参考指标。
Objective:The aim of the study was to investigate the diagnostic value of glucose transporter 1(GLUT1)gene expressionin differentiating malignant thyroid nodules from benign ones. Methods:Reverse transcription Quantitative Real-time PCR(RT-q PCR)was used to detect the expression of GLUT1 m RNA in 112 thyroid nodules(42 benign nodules and 70 malignant ones)and 52 peripheral normal thyroid cells of fine needle aspiration(FNA)specimens. Furthermore,immunohistochemistry(IHC)was used todetect the expression of GLUT1 protein in postoperative thyroid nodule tissues. Receiver operating characteristic(ROC)curve wasplotted to evaluate the diagnostic performance of GLUT1 gene in diagnosing thyroid carcinoma. Results:The expression of GLUT1 m RNA can be detected in FNA specimens,and it was in line with the expression of GLUT1 protein in IHC. PCR results showed thatthere was no significant difference in the expression of GLUT1 m RNA between benign nodules and normal thyroid cells(P > 0.05).Compared to benign nodules,the expression of GLUT1 m RNA in thyroid cancer increased significantly(P < 0.001). The sensitivity,specificity and area under the curve(AUC)of GLUT1 gene in the diagnosis of thyroid cancer were 62.9%,92.9% and 0.797,respectively. The expression of GLUT1 gene in thyroid cancer was not correlated with sex,age,tumor size,number of nodules,BRAFV600 Emutation or lymph node metastasis(P > 0.05),but significantly correlated with AJCC staging(P < 0.001). Conclusion:GLUT1 gene detection had high specificity in diagnosing thyroid cancer,making it an important reference for the preoperativelydifferentiation of benign and malignant lesions.
Objective:The aim of the study was to investigate the diagnostic value of glucose transporter 1(GLUT1)gene expressionin differentiating malignant thyroid nodules from benign ones. Methods:Reverse transcription Quantitative Real-time PCR(RT-q PCR)was used to detect the expression of GLUT1 m RNA in 112 thyroid nodules(42 benign nodules and 70 malignant ones)and 52 peripheral normal thyroid cells of fine needle aspiration(FNA)specimens. Furthermore,immunohistochemistry(IHC)was used todetect the expression of GLUT1 protein in postoperative thyroid nodule tissues. Receiver operating characteristic(ROC)curve wasplotted to evaluate the diagnostic performance of GLUT1 gene in diagnosing thyroid carcinoma. Results:The expression of GLUT1 m RNA can be detected in FNA specimens,and it was in line with the expression of GLUT1 protein in IHC. PCR results showed thatthere was no significant difference in the expression of GLUT1 m RNA between benign nodules and normal thyroid cells(P > 0.05).Compared to benign nodules,the expression of GLUT1 m RNA in thyroid cancer increased significantly(P < 0.001). The sensitivity,specificity and area under the curve(AUC)of GLUT1 gene in the diagnosis of thyroid cancer were 62.9%,92.9% and 0.797,respectively. The expression of GLUT1 gene in thyroid cancer was not correlated with sex,age,tumor size,number of nodules,BRAFV600 Emutation or lymph node metastasis(P > 0.05),but significantly correlated with AJCC staging(P < 0.001). Conclusion:GLUT1 gene detection had high specificity in diagnosing thyroid cancer,making it an important reference for the preoperativelydifferentiation of benign and malignant lesions.
引文
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[11]Grabellus F,Worm K,Schmid KW,et al.The BRAFV600E mutation in papillary thyroid carcinoma is associ-ated with glucose transporter 1 overexpression[J].Thy-roid,2012,22(4):377-382
[12]Durante C,Puxeddu E,Ferretti E,et al.BRAF mutationsin papillary thyroid carcinomas inhibit genes involved iniodine metabolism[J].J Clin Endocrinol Metab,2007,92(7):2840-2843
[13]Grabellus F,Nagarajah J,Bockisch A,et al.Glucose trans-porter 1 expression,tumor proliferation,and iodine/glu-cose uptake in thyroid cancer with emphasis on poorly dif-ferentiated thyroid carcinoma[J].Clin Nucl Med,2012,37(2):121-127
[14]Kim S,Chung JK,Min HS,et al.Expression patterns ofglucose transporter-1 gene and thyroid specific genes inhuman papillary thyroid carcinoma[J].Nucl Med Mol Im-aging,2014,48(2):91-97
[15]Nahm JH,Kim HM,Koo JS.Glycolysis-related protein expression in thyroid cancer[J].Tumour Biol,2017,39(3):1010428317695922
[16]Mori Y,Tsukinoki K,Yasuda M,et al.Glucose transporter type 1 expression are associated with poor prognosis in patients with salivary gland tumors[J].Oral Oncol,2007,43(6):563-569
[2]Matsuzu K,Segade F,Matsuzu U,et al.Differential ex-pression of glucose transporters in normal and pathologicthyroid tissue[J].Thyroid,2004,14(10):806-812
[3]Jozwiak P,Krzeslak A,Pomorski L,et al.Expression ofhypoxia-related glucose transporters GLUT1 and GLUT3in benign,malignant and non-neoplastic thyroid lesions[J].Mol Med Rep,2012,6(3):601-606
[4]Yasuda M,Ogane N,Hayashi H,et al.Glucose transporter-1 expression in the thyroid gland:clinicopathological sig-nificance for papillary carcinoma[J].Oncol Rep,2005,14(6):1499-1504
[5]Tuttle RM,Haugen B,Perrier ND.Updated AmericanJoint Committee on cancer/tumor-node-metastasis stagingsystem for differentiated and anaplastic thyroid cancer(eighth edition):what changed and why?[J].Thyroid,2017,27(6):751-756
[6]Zhang YZ,Xu T,Cui D,et al.Value of TIRADS,BSRTC and FNA-BRAFV600Emutation analysis in differentiatinghigh-risk thyroid nodules[J].Sci Rep,2015,5:16927
[7]Cibas ES,Ali SZ.The bethesda system for reporting thy-roid cytopathology[J].Thyroid,2009,19(11):1159-1165
[8]Remmele W,Stegner HE.Recommendation for uniformdefinition of an immunoreactive score(IRS)for immuno-histochemical estrogen receptor detection(ER-ICA)inbreast cancer tissue[J].Pathologe,1987,8(3):138-140
[9]Ngo DC,Ververis K,Tortorella SM,et al.Introduction tothe molecular basis of cancer metabolism and the War-burg effect[J].Mol Biol Rep,2015,42(4):819-823
[10]Chandan VS,Faquin WC,Wilbur DC,et al.The role ofimmunolocalization of CD57 and GLUT-1 in cell blocksin fine-needle aspiration diagnosis of papillary thyroid car-cinoma[J].Cancer,2006,108(5):331-336
[11]Grabellus F,Worm K,Schmid KW,et al.The BRAFV600E mutation in papillary thyroid carcinoma is associ-ated with glucose transporter 1 overexpression[J].Thy-roid,2012,22(4):377-382
[12]Durante C,Puxeddu E,Ferretti E,et al.BRAF mutationsin papillary thyroid carcinomas inhibit genes involved iniodine metabolism[J].J Clin Endocrinol Metab,2007,92(7):2840-2843
[13]Grabellus F,Nagarajah J,Bockisch A,et al.Glucose trans-porter 1 expression,tumor proliferation,and iodine/glu-cose uptake in thyroid cancer with emphasis on poorly dif-ferentiated thyroid carcinoma[J].Clin Nucl Med,2012,37(2):121-127
[14]Kim S,Chung JK,Min HS,et al.Expression patterns ofglucose transporter-1 gene and thyroid specific genes inhuman papillary thyroid carcinoma[J].Nucl Med Mol Im-aging,2014,48(2):91-97
[15]Nahm JH,Kim HM,Koo JS.Glycolysis-related protein expression in thyroid cancer[J].Tumour Biol,2017,39(3):1010428317695922
[16]Mori Y,Tsukinoki K,Yasuda M,et al.Glucose transporter type 1 expression are associated with poor prognosis in patients with salivary gland tumors[J].Oral Oncol,2007,43(6):563-569