Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Clin Genet. 2019 Nov;96(5):418-428. doi: 10.1111/cge.13609. Epub 2019 Jul 31.
The mechanism of papillary thyroid cancer (PTC) has shown numerous recurrently mutated genes, but the discovery of abnormal expression of novel tumor suppressor genes has been slow. The aim of our study is to explore the biological functions of SDPR in thyroid cancer. We reanalyzed the RNA-Seq data of PTC from The Cancer Genome Atlas (TCGA) database and found that serum deprivation response (SDPR) was significantly downregulated in PTC. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was performed to assess the expression of SDPR. Both loss- and gain-of-function experiments, and flow cytometry were performed to investigate the functions. SDPR was significantly downregulated in PTC. Reduced expression of SDPR was associated with larger tumor size, more serious lymph node metastasis, and advanced American Joint Committee on Cancer (AJCC) stage. Patients with lower SDPR expression had a shorter recurrence-free survival. SDPR expression and AJCC stage were independent predictors of poor recurrence-free survival (RFS). Moreover, cell proliferation, colony formation, and migration were inhibited after SDPR overexpression, whereas knockdown of SDPR exerted an oncogenic effect. SDPR induction also initiated the mesenchymal-epithelial transition, alongside suppressing AKT signaling and cyclin family expression. Apart from DNA methylation, LOC105373813, may also co-regulate SDPR expression by forming a stable hybrid with SDPR messenger RNA. Our study indicated that SDPR may function as a potential prognostic marker in PTC.
甲状腺癌（PTC）的发病机制已显示出许多反复突变的基因，但异常表达的新型肿瘤抑制基因的发现一直较为缓慢。我们的研究旨在探索 SDPR 在甲状腺癌中的生物学功能。我们重新分析了来自癌症基因组图谱（TCGA）数据库的 PTC 的 RNA-Seq 数据，发现血清剥夺反应（SDPR）在 PTC 中显著下调。采用定量逆转录聚合酶链反应（RT-qPCR）来评估 SDPR 的表达。通过进行失活和功能获得实验以及流式细胞术来研究其功能。在 PTC 中，SDPR 表达显著下调。SDPR 表达降低与肿瘤体积较大、淋巴结转移更严重以及美国癌症联合委员会（AJCC）分期较高相关。SDPR 表达水平较低的患者无复发生存时间较短。SDPR 表达和 AJCC 分期是无复发生存（RFS）不良的独立预测因子。此外，过表达 SDPR 可抑制细胞增殖、集落形成和迁移，而敲低 SDPR 则发挥致癌作用。SDPR 诱导还启动了间充质上皮转化，同时抑制 AKT 信号和细胞周期家族的表达。除了 DNA 甲基化，LOC105373813 还可能通过与 SDPR 信使 RNA 形成稳定的杂交来共同调节 SDPR 的表达。我们的研究表明，SDPR 可能作为 PTC 的一个潜在预后标志物。
