| Thyroid carcinoma is one of the most common type of malignant endocrine neoplasia,the incidence is growing rapidly in recent years[1].The study found that thyroid carcinoma is the result of multiple factors,genetic,environmental and personal behavior as the combined effect,but its exact pathogenesis is unclear[2].Therefore investigate the cause of thyroid cancer and the factor affecting its invasion and metastasis has an important significance of the treatment of thyroid cancer and improve the prognosis of patients.Transforming growth factor β1(TGF-β1)is a typical multifunctional cytokine,has a regulatory role of cell proliferation and differentiation,angiogenesis,immunosuppression,extracellular matrix and fiber formation.It has twoway adjustment on cell proliferation,it has inhibition in normal and early tumor cells’ universal,but in advanced cancer cells,it helps tumors evade immune surveillance and thus suppress the immune system of cancer killer effect.Fibroblast growth factor receptor 4(FGFR-4)belongs to an important member of the family of receptor tyrosine kinases(PTK),combine with the ligand fibroblast growth factor(FGF),has the regulation of a large class of cell proliferation,apoptosis,migration and angiogenesis process.In a variety of tumor cells are present FGF/FGFR signaling pathway deregulation,which may play an important role in tumor development process by promoting angiogene sis or direct stimulation of tumor growth.The purpose of this study is to explore these two factors in papillary thyroid carcinoma(PTC)in the expression of its relevance,and its relationship with clinicopathological features of its relevance,thus insight into the occurrence,development and prognosis of PTC,thus guide the development of multitarget anti-drug for PTC.Objective:In this study, we analyzed the expression level of FGFR-4 and TGF-β1 in PTC paired adjacent normal thyroid tissue and normal thyroid tissue to assess if this was associated with selected clinicopathogenetic features in order to guide the diagnosis and treatment and prognosis of PTC. The relevance of FGFR-4 and TGF-β1 in PTC were analyzed.The ultimate goal is to find the high activity and low toxicity multi-targets agents for PTC.Method:1 89 cases of PTCs and 30 cases of normal thyroid tissues were used in this study with immunohistochemistry staining to detect the expression of FGFR-4 and TGF-β1,the data were compared with clinical pathological datas of PTC.2 The expression of FGFR-4 and TGF-β1 in 45 cases of PTCs and 30 cases of adjacent tissues of thyroid tumor were detected by Western blot.Result:1 FGFR-4 protein was mainly expressed in the membrane or cytoplasm of tumor cells and small quantity of nucleus(Fig.7).Statistical analysis revealed that the positive rate of FGFR-4 in PTCs was 86.5%,the positive rate in adjacent normal tissues was 13.3%(Fig.6).The average IOD statistics showed that the difference of FGFR-4 expression in PTC and adjacent normal tissues was statistically significant(t=4.310,P=0.002)(Table 2)。2 The positive expression of TGF-β1 protein was mainly in the cytoplasm of tumor cells(Fig.4).Statistical analysis revealed that the positive rate of TGF-β1 in PTCs was 77.5%,the positive rate in adjacent normal tissues was 6%(Fig.3).The average IOD statistics showed that the difference of TGF-β1 expression in PTC and adjacent normal tissues was statistically significant(t=-5.782,P=0.000)(Table 1)。3 Statistical analysis revealed that the expression of FGFR-4 in PTCs is not correlated to the gender,age and tumor size(P>0.05),but it was correlated with differentiation expression of tumor,TNM stage and lymph node metastasize(P<0.01). The positive expression of FGFR-4 protein in lymph node metastasize of PTC(93.7%)was significant highe than that in without(76.2%)(P< 0.05). The positive stained rate of FGFR-4 was significant higher inadvanced stage(III,IV)( 90.2%)than that in early stage(I,II)( 71.8%)(P<0.05). 4 The positive expression of TGF-β1 in PTCs has no correlated with4 The positive expression of TGF-β1 in PTCs has no correlated with gender,age or tumor size(P>0.05),but it was correlated with differentiation expression of tumor,TNM stage and lymph node metastasize(P<0.01). The positive expression of TGF-β1 protein in lymph node metastasize of PTC(93.6%)was significant higher than that in without(59.5%)(P<0.05). The positive stained rate of TGF-β1 was significant higher in advanced stage(III,IV)( 97.5%)than th at in early st ag e(I,II)( 79.5 %)( P<0.01).5 Measuring the average spectral density of the TGF-β1 and FGFR-4 immunohistochemical staining for statistical analysis and correlation,non-linear relationship between the value of the average optical density of TGF-β1 and FGFR-4.Spearman correlation analysis was applied to test its correlation coefficients rs=0.327,both showed a significant positive correlation(P<0.05), the results in table 4.6 In the adjacent normal and varying degrees of differentiation of papillary thyroid carcinoma, the protein expression of TGF-β1 and FGFR-4 in cancer tissues(FGFR4well differentiated groups2952.77±2.49,differentiation among groups4037.9±3.05,poorly differentiated group 5228.57±1.89; TGF-β1well differentiated groups2952.77±2.49,differentiation among groups 4037.9±3.05,poorly differentiated expression group5228.57±1.89)was significantly higher than in adjacent normal tissue(906.8±2.72),with carcinoma degree of differentiation decreased significantly upregulated,as shown table 5,the test results consistent with the results of immunohistochemistry.Conclusions:1 Compared with normal thyroid tissues,the expression of TGF-β1 and FGFR-4 protein were significant higher,which showed that the high expression may play a important role in the oncogenesis of PTC.2 The expression rates of TGF-β1 and FGFR-4 were correlated with differentiation expression of tumor,TNM stage and lymph node metastasize,and had nothing to do with sex,age or tumor size,.The result indicated that up-regulated TGF-β1 and FGFR-4 may play a role in PTC development.3 The protein expression of TGF-β1 and FGFR-4 was positively correlated, which suggesting that both the development and invasion correlated with PTC tumorigenesis. |
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