FAM172A Promotes Follicular Thyroid Carcinogenesis And May Be Used As A Preoperative Diagnostic Marker Of Malignant Thyroid Tumors

Purpose:We aimed to uncover the role of family with sequence similarity 172-member A(FAM172A)in the pathogenesis of FTC and evaluate its value in differential diagnosis between benign and malignant thyroid follicular lesions.Materials and Methods:1.FAM172 A expression was performed by immunoblotting and immunohistochemistry(IHC).Based on IHC of FAM172 A in 120 formalinfixed paraffin-embedded(FFPE)tissues,a receiver operating characteristic(ROC)curve was used to identify optimal cut-off points of FAM172 A scores for distinguishing benign from malignant thyroid follicular lesions.2.Cell Counting Kit-8 assay(CCK8),Clone-formation and Transwell assays were performed to detect the ability of proliferation,migration and invasion of cells,respectively.Immunoblotting,IHC and nude mouse tumorigenicity assays were used to investigate the role of FAM172 A in pathogenesis of FTC in vivo and vitro.Next-generation sequencing technology was performed in human FTC-238 cells,shFAM172A-FTC-238 cells,normal human thyroid cell line Nthy-ori 3-1 and human FTC and adjacent-carcinoma tissue samples,respectively.3.The value of FAM172 A in differential diagnosis for FTC before operation was assessed using the cut-off points of FAM172 A scores in 86 fine-needle aspiration biopsy(FNAB)samples.Results:1.FAM172 A was highly expressed in FTC tissues.The FAM172 A immunohistochemistry scores of 3.5 had 92% sensitivity and 63% specificity to separate malignant from benign/borderline thyroid tumors in postoperative FFPE samples,2.FAM172 A was highly expressed in FTC cell lines FTC-133 and FTC-238.Downexpression of FAM172 A in both FTC-133 and FTC-238 cells showed obviously inhibited the proliferation,invasion and migration than NC-transfected cells(p<0.05)respectively,whereas the overexpression of FAM172 A in Nthy-ori 3-1 cells promotes the proliferation,invasion and migration than negative control NC-transfected cells(p<0.05).Subcutaneous tumorigenesis in nude mice showed that knockdown of FAM172 A inhibited tumor growth and progression in vivo.Downregulation of FAM172 A inhibited the proliferation,invasion and migration of FTC cells through Erk1/2 and JNK/c-JUN pathways.3.The FAM172 A immunohistochemistry scores of 3.5 had 82% sensitivity and 78% specificity in preoperative FNAB samples,respectively.Conclusions:1.The expression of FAM172 A in thyroid follicular carcinoma tissues was higher than that in adjacent tissues;the expression of FAM172 A in human thyroid follicular carcinoma cell lines FTC-133 and FTC-238 was higher than that in human thyroid normal cell line Nthy-ori-3-1;the expression of FAM172 A in thyroid follicular carcinoma tissues is higher than follicular tumor of uncertain malignant potential and thyroid adenoma.2.Knockdown of FAM172 A can inhibite the proliferation,invasion and migration in vivo and vitro.Meanwhile,FAM172 A plays an important role in the pathogenesis of FTC through Erk1/2 and JNK/c-JUN pathways.3.FAM172 A may be used as a potential marker for preoperative diagnosis of malignant thyroid tumors based on the IHC results of thyroid FNAB samples and had 82% sensitivity and 78% specificity.