Correlation study on the expression of TFCP2L1,DUSP26,and MLKL proteins in differentiated thyroid cancer with clinicopathological characteristics and the efficacy of iodine therapy

WANG Jian; LIU Haiyang; ZHANG Xuemei; TONG Rui

doi:10.3969/j.issn.1009-0460.2025.11.009

Abstract：Objective To explore the correlation between the expression of transcription factor CP2-like 1(TFCP2L1),dual-specificity phosphatase 26(DUSP26),and mixed lineage kinase domain-like(MLKL)proteins in differentiated thyroid cancer and the clinical pathological characteristics as well as the therapeutic efficacy of iodine-131(131I)treatment.Methods A total of 131 patients with differentiated thyroid cancer who underwent radical surgery and received their first 131I treatment from March 2021 to March 2024 in Qinhuangdao Hospital of Dongfang Hospital were prospectively selected as the research subjects.The therapeutic efficacy of 131I treatment in differentiated thyroid cancer patients was evaluated.91 patients were included in the 131I effective treatment group,and 40 patients with differentiated thyroid cancer were included in the 131I ineffective treatment group.The expression of TFCP2L1,DUSP26,and MLKL proteins in differentiated thyroid cancer was detected by immunohistochemistry.Multivariate Logistic regression analysis was used to analyze the influencing factors of ineffective 131I treatment in differentiated thyroid cancer patients.The predictive value of TFCP2L1,DUSP26,and MLKL for ineffective 131I treatment in differentiated thyroid cancer patients was evaluated by receiver operating characteristic(ROC)curve.Results In patients with differentiated thyroid carcinoma,the mRNA expression levels of TFCP2L1 and MLKL in tumor tissues were higher than those in adjacent non-tumor tissues,whereas DUSP26 mRNA expression was lower in tumor tissues(all P<0.05).The positive immunohistochemical expression rates of TFCP2L1 and MLKL were significantly higher in tumor tissues than in non-tumor tissues,while the positive rate of DUSP26 was significantly lower(all P<0.05).Expression levels of TFCP2L1,DUSP26,and MLKL were associated with the presence of multifocal disease and lymph node metastasis in differentiated thyroid carcinoma patients(all P<0.05).Compared with the 131I effective-treatment group,patients in the 131I ineffective-treatment group had higher proportions of multifocal disease,lymph node metastasis,131I dose>100 mCi,and higher levels of TFCP2L1 and MLKL,which were risk factors for 131I treatment ineffectiveness.DUSP26 levels were lower than in the effective group and acted as a protective factor(all P<0.05).The combined model of TFCP2L1,DUSP26,and MLKL for predicting 131I treatment effects in differentiated thyroid carcinoma yielded an area under the curve(AUC)of 0.950(95%CI:0.915-0.985),which was significantly superior to the AUCs of any single marker-TFCP2L1(Z=2.447,P<0.05),DUSP26(Z=2.382,P<0.05),or MLKL(Z=3.101,P<0.05).Conclusion The positive expression rates of TFCP2L1,MLKL in cancer tissue of patients with differentiated thyroid cancer were high,and the positive expression rates of DUSP26 were low,which were related to the clinicopathological characteristics of multifocal lesions and lymph node metastasis.The combined expression of the three factors had a high value in predicting the treatment effects of 131I in patients with differentiated thyroid cancer.