甲状腺髓样癌中PTEN/PI3K/AKT通路的变化及临床病理意义

Changesof PTEN/PI3K/Akt pathway in medullary thyroid carcinoma and itsclinicopathological significance.

目的研究甲状腺髓样癌中第10号染色体缺失的磷酸酶及张力蛋白同源蛋白(PTEN)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)通路的变化及临床病理意义。方法采用回顾性研究,选择2016年1月至2020年6月期间在中国人民解放军南部战区总医院接受手术切除的121例甲状腺髓样癌患者,收集甲状腺髓样癌组织及癌旁组织,检测PTEN的阳性表达率、mRNA表达水平及p-PI3K、p-AKT的蛋白表达水平,随访患者的无病生存情况。结果甲状腺髓样癌组织中PTEN的阳性率、mRNA表达水平为31.40%、0.72±0.14,均低于癌旁组织(65.29%、1.00±0.19),p-PI3K、p-AKT的表达水平分别为1.03±0.19、1.09±0.18,均高于癌旁组织(0.73±0.17、0.52±0.10),差异均有统计学意义(P<0.05)。甲状腺髓样癌中PTEN的mRNA表达水平与p-PI3K、p-AKT的表达水平呈负相关(r=-0.386、-0.427,P<0.05)。PTEN阳性表达的甲状腺髓样癌中p-PI3K、p-AKT的表达水平分别为0.64±0.13、0.41±0.08,低于PTEN阴性表达的甲状腺髓样癌(0.77±0.19、0.57±0.12),差异均有统计学意义(P<0.05)。TTNMⅢ~Ⅳ期甲状腺髓样癌中PTEN的阳性率、mRNA表达水平为23.53%、0.67±0.13,均低于Ⅰ~Ⅱ期甲状腺髓样癌(41.51%、0.79±0.16),差异均有统计学意义(P<0.05)。甲状腺髓样癌中PTEN阴性表达患者的累积无病生存率低于PTEN阳性表达患者,差异有统计学意义(P<0.05)。结论甲状腺髓样癌中PTEN表达降低与下游PI3K/AKT通路激活、TNM分期进展、预后不良有关。

Objective To study the changes of phosphatase andphosphatase and tensin homolog deleted on chromosome ten(PTEN)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in medullary thyroid carcinomaand clinicopathological significance.Methods Using a retrospective study,121 patients with medullary thyroid carcinoma who underwent surgical resection in General Hospital of Southern Theater Command,PLA from January 2016 to June 2020 were selected.Medullary thyroid carcinoma tissues and adjacent tissues were collected and the positive expression rate and mRNA expression level of PTEN,the protein expression levels of p-PI3K and p-AKT were detected.The disease-free survival of patients was followed up.Results The positive rate and mRNA expression level of PTEN in medullary carcinoma were 31.40%,0.72±0.14,which were lower than the adjacent tissue(65.29%,1.00±0.19),the expression level of p-PI3K and p-AKT were 1.03±0.19,1.09±0.18,respectively which were higher than those in the adjacent tissue(0.73±0.17,0.52±0.10),the differences were statistically significant(P<0.05).The mRNA expression of PTEN in medullary thyroid carcinoma was negatively correlated with the expression of p-PI3K and p-AKT(r=-0.386,-0.427,P<0.05).The expression levels of p-PI3K and p-AKT in PTEN positive medullary thyroid carcinoma were 0.64±0.13,0.41±0.08,respectively which were lower than those in PTEN negative medullary thyroid carcinoma(0.77±0.19,0.57±0.12),the differences were statistically significant(P<0.05).The positive expression rate and mRNA expression level of PTEN in TNM stageⅢ~Ⅳmedullary thyroid carcinoma were 23.53%,0.67±0.13,which were lower than those in stageⅠ~Ⅱmedullary thyroid carcinoma(41.51%,0.79±0.16),the differences were statistically significant(P<0.05).The cumulative disease-free survival rate of patients with negative PTEN expression in medullary thyroid carcinoma was lower than that of patients with positive PTEN expression,the differences were statistically significant(P<0.05).Conclusion The decreased expression of PTEN in medullary thyroid carcinoma is related to the activation of downstream PI3K/Akt pathway,the progress of TNM stage and poor prognosis.