三叶因子3在甲状腺乳头状癌中的表达及临床意义
Expression and clinical significance of trefoil factor 3 in patiens with papillary thyroid carcinoma
目的 探讨甲状腺乳头状癌(PTC)患者血清与组织中三叶因子3(TFF3)的表达水平及意义。方法 收集甲状腺肿瘤患者153例,其中乳头状癌组66例、腺瘤组51例、乳头状增生组36例,正常组153例(来源于每例标本的正常甲状腺组织)。16例正常人血清标本作为ELISA检测的
正常组。采用免疫组织化学SP法和原位杂交技术检测甲状腺手术标本中TFF3蛋白和mRNA的表达;ELISA检测血清TFF3浓度。结果 1. TFF3蛋白和mRNA均表达于细胞质,呈棕黄色颗粒。66例乳头状癌TFF3表达阳性率92.42%;36例乳头状增生阳性率47.22%;51例腺瘤阳性率31.37%;正
常组阳性率25.40%;各组TFF3 mRNA阳性率略低于其蛋白,且与蛋白表达呈正相关(P.<0.0001);甲状腺癌组积分吸光度显著高于其他3组(P<0.01); 2. 甲状腺乳头状癌中TFF3及mRNA高表达率与TNM分期和淋巴结转移有关(P<0.01); 3. 甲状腺癌组血清TFF3浓度明显高于乳头
状增生组、腺瘤组和健康对照组(P<0.001)。血清TFF3浓度在甲状腺癌组织阳性组明显高于阴性组(P<0.05)。结论 甲状腺乳头状癌高表达 TFF3蛋白及mRNA,检测血清TFF3浓度可能成为诊断甲状腺乳头状癌的筛选指标。
Objective To investigate the expression and significance of trefoil factor 3(TFF3) in serum and tissue of patients with papillary thyroid carcinoma.Methods A total of 153 patients with thyroid tumor were divided into papillary thyroid carcinoma
(PTC) group(PTC,n=46),adenoma group(A,n=51),papillary hyperplasia group(PH,n=36) and normal group,(N,n=153, normal thyroid tissue of every specimen). Sixteen normal human were served as the normal group in ELISA.The expressions of TFF3 protein and mRNA in
surgical specimens were detected by immunohistochemistry(IHC) SP, in situ hibridazation (ISH) and ELISA method was used to determine the serum TFF3 level. Results 1. The positive profiless of TFF3 protein and mRNA were brown granules in cytoplasm. The positive
rate of TFF3 in 66 PTC group, 36 PH group, 51 A group and 153 N group were 92.42%, 47.22%,31.37% and 25.40% respectively.There was a positive correlation between expression of TFF3 mRNA and protein,though a little lower of TFF3 mRNA(P<0.0001). The
integral absorbance (IA) of TFF3 protein and mRNA in PTC was higher those in than other three groups (P<0.01). 2. The high expression rate of TFF3 protein/mRNA in patients with thyroid carcinoma was correlated with the TNM stage and lymph node metastasis
(P<0.01). 3. The concentration of TFF3 in serum with thyroid carcinoma was the highest among the four groups(P<0.001). Serum concentrations of TFF3 in surgical specimens positive group was obviously higher than that in the negative group (P<0.05). Conclusion
TFF3 protein/mRNA expresses strongly in PTC tissues. Detection of the serum TFF3 concentration may be a reference index in diagnosis of thyroid carcinoma.
三叶因子3 / 甲状腺乳头状癌 / 免疫组织化学 / 原位杂交 / 酶联免疫吸附试验 / 人
Trefoil factor 3 / Papillary thyroid carcinoma / Immunohistochemistry / In situ hybridization / Enzymelinked immunoadsordent assay / Human
[1]Thim L. A new family of growth factor-like peptides: “trefoil” disulphide loop structures as a common feature in breastcancer associated peptide (pS2), pancreatic spasmolytic polypeptide (PSP), and frog skin peptides (spasmolysins)[J]. FEBSLett,1989,250 (1):85-90.
[2]Aikou S, Ohmoto Y, Gunji T,et al. Tests for serum levels of trefoil factor family proteins can improve gastric cancer screening[J]. Gastroenterology,2011,141(3):837-845.e1-7.
[3]Vestergaard EM, Nexф E, Tфrring N, et al. Promoter hypomethylation and upregulation of trefoil factors in prostate cancer[J]. Int J Cancer,2010,127(8):1857-1865.
[4]Takano T,Miyauchi A,Yoshida H,et al.High-throughput differential screening of mRNA by serial analysis of gene expression:decreased expression of trefoil factor 3 mRNA in thyroid follicular carcinomas[J].Br J Cancer,2004,90(8):1600-1605.
[5]Takano T, Yamada H. Trefoil factor 3 (TFF3): a promising indicator for diagnosing thyroid follicular carcinoma[J]. Endocr J,2009,56 (1):9-16.
[6]Griffith,OL, Melck A, Jones SJM, et al. Meta-analysis and meta-review of thyroid cancer gene expression profiling studies identifies important diagnostic biomarkers[J]. J Clin Oncol,2006,24(31):5043-5051.
[7]Vestergaard EM, Poulsen SS, Gr?nbaek H,et al.Development and evaluation of an ELISA for human trefoil factor 3[J]. Clin Chem,2002,48(10):1689-1695.
[8]Liu D, el-Hariry I, Karayiannakis AJ, et al. Phosphorylation of betacatenin and epidermal growth factor receptor by intestinal trefoil factor[J]. Lab Invest,1997,77(6):557-563.
[9]Hawthorn L, Stein L, Varma R, et al. TIMP1 and SERPIN-A overexpression and TFF3 and CRABP1 underexpression as biomarkersfor papillary thyroid carcinoma[J]. Head Neck,2004(12):1069-1083.
[10]Taniguchi K,Takano T,Miyauchi A,et al.Differentiation of follicular thyroid adenoma from carcinoma by means of gene expression profiling with adapter-tagged competitive polymerase chain reaction[J].Oncology,2005,69(5):428-435.
[11]Durand S,Ferraro-Peyret C,Selmi-Ruby S,et al.Evaluation of gene expression profiles in thyroid nodule biopsy material to diagnose thyroid cancer[J].J Clin Endocrinol Metab,2008,93(4):1195-1202.
[12]Krause K,Eszlinger M,Gimm O,et al.TFF3 based candidate gene discrimination of benign and malignant thyroid tumours in a region with borderline iodine deficiency[J].J Clin Endocrinol Metab,2008,93(4):1390-1393.
[13]Qu Y, Yang Y, Ma D, et al. Increased trefoil factor 3 levels in the serum of patients with three major histological subtypes of lung cancer[J]. Oncol Rep,2012,27(4):1277-1283.
[14]Vestergaard EM, Borre M, Poulsen SS,et al.Plasma levels of trefoil factors are increased in patients with advanced prostatecancer[J]. Clin Cancer Res,2006,12(3 Pt 1):807-812.
河北省教育厅重点项目ZD2010101;河北省科技厅12276104D-91;其他(不属于以上基金类别的请自行输入下框)
/
〈 |
|
〉 |