Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Emergency, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Endocr Relat Cancer. 2020 Nov;27(11):657-669. doi: 10.1530/ERC-20-0181.
Our aims were to uncover the role of FAM172A (Family with sequence similarity 172 member A) in the pathogenesis of follicular thyroid carcinoma (FTC) and to evaluate its value in the differential diagnosis between malignant and benign thyroid follicular lesions. FAM172A expression was evaluated by q-PCR, immunoblotting and immunohistochemistry (IHC). The ability of proliferation, migration and invasion of cells were assessed by Cell Counting Kit-8 assay (CCK8), clone-formation and Transwell assays. Nude mouse tumorigenicity assays were used to investigate the role of FAM172A in the pathogenesis of FTC in vivo. The value of FAM172A in the differential diagnosis for FTC was assessed using 120 formalin-fixed paraffin-embedded (FFPE) tissues after the operation and 81 fine-needle aspiration biopsy (FNAB) samples before the operation. FAM172A was highly expressed in FTC tissues and FTC cell lines. Downregulation of FAM172A inhibited the proliferation, invasion and migration of FTC cells through Erk1/2 and JNK pathways. Subcutaneous tumorigenesis in nude mice showed that knockdown of FAM172A inhibited tumor growth and progression in vivo. The FAM172A IHC scores of 3.5 had 92% sensitivity and 63% specificity to separate FTC from benign/borderline thyroid follicular lesions, and 92% sensitivity and 80% specificity to discriminate FTC from benign thyroid follicular lesions in postoperative FFPE samples. The corresponding values were 75 and 78%, and 75 and 89% in preoperative FNA samples, respectively. FAM172A plays an important role in the pathogenesis of FTC through Erk1/2 and JNK pathways. FAM172A may be a potential marker for the preoperative diagnosis of FTC based on the IHC results of thyroid FNAB samples.
我们的目的是揭示 FAM172A（家族与序列相似性 172 成员 A）在滤泡状甲状腺癌（FTC）发病机制中的作用，并评估其在恶性和良性甲状腺滤泡性病变鉴别诊断中的价值。通过 q-PCR、免疫印迹和免疫组织化学（IHC）评估 FAM172A 的表达。通过细胞计数试剂盒-8 测定法（CCK8）、克隆形成和 Transwell 测定评估细胞增殖、迁移和侵袭的能力。使用裸鼠肿瘤发生测定法研究 FAM172A 在体内 FTC 发病机制中的作用。使用手术后 120 例福尔马林固定石蜡包埋（FFPE）组织和手术前 81 例细针抽吸活检（FNAB）样本评估 FAM172A 在 FTC 鉴别诊断中的价值。FAM172A 在 FTC 组织和 FTC 细胞系中高表达。通过 Erk1/2 和 JNK 途径下调 FAM172A 抑制 FTC 细胞的增殖、侵袭和迁移。裸鼠皮下肿瘤生成表明，FAM172A 的敲低抑制了体内肿瘤的生长和进展。FAM172A 的 IHC 评分为 3.5 时，对良性/交界性甲状腺滤泡性病变与 FTC 进行分离的敏感性为 92%，特异性为 63%，对术后 FFPE 样本中 FTC 与良性甲状腺滤泡性病变进行分离的敏感性为 92%，特异性为 80%。术前 FNA 样本的相应值分别为 75%和 78%，75%和 89%。FAM172A 通过 Erk1/2 和 JNK 途径在 FTC 的发病机制中发挥重要作用。FAM172A 可能是基于甲状腺 FNAB 样本的 IHC 结果进行术前 FTC 诊断的潜在标志物。
