The Relationship Between PI3K/Akt Signal Transduction Pathway And Thyroid Nodule

Objective:Abroad research displayed the abnormal activation of PI3K/Akt signal transduction pathway in thyroid nodule. Our research aimed to investigate the expression of the ralated molecular in this pathway, and elucidate its etiology and the pathogenesis, and further explore the molecular biological prevention and treatment strategy of thyroid nodular disease.Methods; The study subjects were devided into two major groups:the thyroid nodule group and the normal control group. The patients selected from the Affiliated Hospital of Jining Medical College were experienced partial or whole thyroidectomy in the Breast and Thyroid surgical department during the period of Dec 2008 and Aug 2009, of which were divided into three subgroups:the papillary thyroid carcinima group, the thyroid follicular adenoma group and the nodular goiter group, each group includes 30 cases. The thyroid tissue sample of the normal control group was taken just besides the follicular adenoma patients who were experieced the adenoma resection operation. Each group never received chemotherapy, radiotherapy or endocrine hormone replacement therapy. We also recorded the patient's basic information such as the name, sex, age, lymph node metastasis condition and amicula infiltration degree of papillary thyroid carcinima. We collected about 200mg fresh tissue of each specimen into two EP tubes respectively, which were throwed into liquid nitrogen within ten minutes, and then stored in -80℃refrigerator, and we also collected the paraffin block of the specimen simultaneously. RT-PCR method was used to detect the expressions of PI3KmRNA, AktmRNA of PI3K/Akt signal transduction pathway in all the groups. Western-blot and immunohistochemistry methods were used to measure the protein content of PI3K, Akt and p-Akt semi-quantitatively.Results:The general information showed the average age of normal group, nodular goiter and papillary thyroid carcinima were 37.47±6.79, 40±8.51and 37.13±6.36 respectively. The sex and age of each group hadn't show any statistical significance among these group(P>0.05). The content of PI3KmRNA and AktmRNA in thyroid nodules is higher than that of the normol thyroid tissue, which showed a statistical significance(P<0.05). The results of immunohistochemistry, Western Blot test discovered that PI3K, Akt and p-Akt protein content in the thyroid nodule group was higher than that of normal control group(P<0.05), further analysis showed that the content of PI3K, Akt and p-Akt protein is decreased gradually in the papillary thyroid carcinima, thyroid follicular adenoma and nodular goiter group, but the content of PI3K, Akt and p-Akt protein in thyroid follicular adenoma group campared with the nodular goiter group had no statistical significance(P>0.05). The correlation analysis showed that the level of PI3K and Akt in thyroid tissue was positive correlated(r=0.992,P<0.001), so did the PI3K and pAkt(r=0.974, P<0.001), Akt and pAkt(r=0.976, P<0.001), PI3KmRNA and AktmRNA (r=0.978, P<0.001). The assay result of PI3KmRNA was in coincidence with AktmRNA in these four groups, so did the PI3K, Akt and pAkt. The content of PI3K, Akt and pAkt protein were related to the lymph node metastasis and infiltration degree, but had no relationship with the age, sex and pathology staging(P>0.05).Conclusion:①The expression of PI3KmRNA, AktmRNA and the content of PI3K, Akt, pAkt were higher in papillary thyroid carcinima, thyroid follicular adenoma and nodular goiter than those of thyroid normal tissue, which showed PI3K/Akt signal transduction pathway was activated abnormally in thyroid nodule.②The content of PI3KmRNA, AktmRNA and PI3K, Akt and pAkt were the highest in the papillary thyroid carcinima group, which suggested the PI3K/Akt pathway was activated abnormally in malignant tumors of thyroid, and the activited level of this pathway was related to the characteristic feature of thyroid nodule.③The analysis showed that the expression of PI3K, Akt, pAkt were higher in the papillary thyroid carcinima group with the metastasis of lymph node and the extracapsular spread of thyroid carcinima.And hadn't show any statistical significance among the subgroup of different name, sex and age.