Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal.
Cancer Signaling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal.
Endocrine. 2021 Jul;73(1):85-97. doi: 10.1007/s12020-020-02546-4. Epub 2020 Nov 20.
Dynamin-related protein 1 (DRP1), a mitochondrial fission protein, and its active form phosphorylated at Serine 616 (S616-p-DRP1) have been increasingly associated with tumorigenesis and invasion in various tumor models, including oncocytic thyroid cancer (TC). In this study, the expression of DRP1 and S616-p-DRP1 and its relationship with patients' clinicopathological characteristics, tumor genetic profiles, and clinical outcomes were assessed in a large series of follicular cell-derived TC (FCDTC).
Retrospective biomarker study characterizing the clinicopathological and immunochemistry DRP1 and S616-p-DRP1 expression of a series of 259 patients with FCDTC followed in two University Hospitals.
DRP1 expression was positive in 65.3% (169/259) of the cases, while the expression of the S616-p-DRP1 was positive in only 17.3% (17/98). DRP1-positive expression was significantly associated with differentiated tumors (67.7 vs. 48.0%; P = 0.049), non-encapsulated tumors (73.8 vs. 57.4%; P = 0.011) and thyroid capsule invasion (73.4 vs. 57.5%; P = 0.013). S616-p-DRP1-positive expression was significantly associated with tumor infiltrative margins (88.9 vs. 11.1%; P = 0.033), thyroid capsule invasion (29.8 vs. 3.1%; P = 0.043), lymph node metastases (23.3 vs. 8.1%; P = 0.012), and higher mean cumulative radioiodine dosage (317.4 ± 265.0 mCi vs. 202.5 ± 217.7 mCi; P = 0.038). S616-p-DRP1 expression was negatively associated with oncocytic phenotype (0.0 vs. 26.2%; P = 0.028).
S616-p-DRP1 is a better candidate than DRP1 to identify tumors with locally invasive behavior. Prospective studies should be pursued to assess S616-p-DRP1 role as a molecular marker of malignancy in TC and in patients' risk assessment.
动力相关蛋白 1（DRP1）是一种线粒体分裂蛋白，其在丝氨酸 616 位磷酸化的活性形式（S616-p-DRP1）与各种肿瘤模型中的肿瘤发生和侵袭的关系越来越密切，包括嗜酸细胞性甲状腺癌（TC）。在这项研究中，我们评估了 DRP1 和 S616-p-DRP1 的表达及其与患者临床病理特征、肿瘤遗传特征和临床结果的关系，研究对象是两家大学医院的 259 例滤泡细胞来源的 TC（FCDTC）患者。
这是一项回顾性生物标志物研究，对 259 例 FCDTC 患者的临床病理和免疫化学 DRP1 和 S616-p-DRP1 表达进行了特征描述。
65.3%（169/259）的病例中 DRP1 表达阳性，而 S616-p-DRP1 表达阳性的比例仅为 17.3%（17/98）。DRP1 阳性表达与分化良好的肿瘤（67.7% vs. 48.0%；P=0.049）、非包膜肿瘤（73.8% vs. 57.4%；P=0.011）和甲状腺包膜侵犯（73.4% vs. 57.5%；P=0.013）显著相关。S616-p-DRP1 阳性表达与肿瘤浸润性边缘（88.9% vs. 11.1%；P=0.033）、甲状腺包膜侵犯（29.8% vs. 3.1%；P=0.043）、淋巴结转移（23.3% vs. 8.1%；P=0.012）和平均累积放射性碘剂量较高（317.4±265.0mCi vs. 202.5±217.7mCi；P=0.038）显著相关。S616-p-DRP1 表达与嗜酸细胞表型呈负相关（0.0% vs. 26.2%；P=0.028）。
S616-p-DRP1 是一种比 DRP1 更好的候选标志物，可用于识别具有局部侵袭性行为的肿瘤。应开展前瞻性研究，以评估 S616-p-DRP1 作为 TC 及患者风险评估中恶性肿瘤分子标志物的作用。
