关键词: 甲状腺乳头状癌, 远处转移, 生化进展, 甲状腺球蛋白倍增时间, T淋巴细胞亚群, 基因突变

Abstract: Background Advanced，especially distant metastatic papillary thyroid carcinoma（DM-PTC）is mainly monitored by serological（thyroglobulin，Tg）and radiological（CT） examinations. Due to the inherent limitations of imaging modalities, such as radiation，expensive price and the complicated distribution of the metastatic lesions，the traditional response evaluation criteria in solid tumors 1.1（RECIST 1.1） often fails to timely detect the changes of DM-PTC. By incorporating the time factors，Tg Doubling Time（TgDT）has gradually demonstrated its role in sensitively monitoring disease changes in PTC. Objective To explore the biochemical progression of DM-PTC and its influencing factors using TgDT as the outcome variable. Methods DM-PTC patients retrospectively were collected and TgDT was calculated using at least three or more suppressed Tg（TSH < 0.1 mIU/L）results within 2-3 years after the last 131I treatment. Patients were divided into TgDT< 3 y group (n=16) and TgDT≥3y group (n=45). Univariate and multivariate logistic regression analyses were used to explore the factors including clinicopathological characteristics and peripheral blood lymphocyte subsets which may affect the biochemical progression. Results TgDT< 3 y group were older at diagnosis，undergone more local operations before the last 131I treatment, had a higher incidence of RAIR，a higher TERT mutation rate and BRAF combined TERT mutation rate, a lower RET fusion rate, a lower percentage of CD3+T cells and CD8+T cells, and a higher percentage of NK cells and CD4/CD8 ratio (all P <0.05). Multivariate Logistic regression analysis showed that low CD8+T cell percentage and BRAF combined TERT mutation were risk factors for the biochemical progression of DM-PTC. Conclusion Multiple factors such as the immune status of a low percentage of CD8+T cells and BRAF combined TERT mutation can affect the biochemical progression of DM-PTC. The detection of lymphocyte subsets and polygenes is of great significance for the disease monitoring and prognosis evaluation of DM-PTC.

Key words: Papillary thyroid carcinoma, Distant metastasis, Biochemical progression, Thyroglobulin doubling time, T lymphocyte subsets, Gene mutation