Xu Qiu, Yang Han, Fan Gai, Zhang Bo, Yu Jinsong, Zhang Zhixin, Jia Guangwei
Department of Thyroid and Breast Surgery, Nanyang First People's Hospital affiliated to Henan University, Nanyang 473012, China; Key Laboratory of Thyroid Tumor Prevention and Treatment, Nanyang First People's Hospital affiliated to Henan University, Nanyang 473012, China.
Department of Endocrinology, Nanshi Hospital of Nanyang, Nanyang 473000, China.
Pathol Res Pract. 2022 Oct;238:154092. doi: 10.1016/j.prp.2022.154092. Epub 2022 Aug 28.
Thyroid cancer is a common malignant tumor with rising incidence worldwide. The purpose of this study was to explore key genes in thyroid cancer. The differentially expressed genes were analyzed according to GEO datasets. PLA2R1 and RASSF9 levels were confirmed by UALCAN and the Human Protein Atlas databases. The disease free survival and linear correlation were analyzed by GEPIA. ROC curve was generated according to The Cancer Genome Atlas (TCGA) database. The methylation level and immune infiltration were analyzed using GSCA platform. PLA2R1, RASSF9 and Wnt/β-catenin-related protein levels were detected by western blotting. Cell proliferation was assessed by 5-ethynyl-2'-deoxyuridine assay. Cell invasion and migration were evaluated by Transwell assay. There were 2 common differentially expressed genes (PLA2R1 and RASSF9) in thyroid cancer from GSE104005, GSE65144 and GSE53157 datasets. Decreased PLA2R1 and RASSF9 were associated with advanced stages and lower disease free survival. PLA2R1 and RASSF9 methylation levels were enhanced in thyroid cancer samples compared with normal samples. PLA2R1 methylation level was negatively correlated to its mRNA level. PLA2R1 and RASSF9 were related to immune infiltration in thyroid cancer. PLA2R1 and RASSF9 expression was associated with radioiodine resistance, and positively correlated to expression of iodide uptake-related factors. Multiple signaling pathways were involved in the action mechanisms of PLA2R1 and RASSF9, including the Wnt/β-catenin signaling. Overexpression of PLA2R1 and RASSF9 inhibited the activation of the Wnt/β-catenin pathway, proliferation, invasion, and migration in thyroid cancer cells. Collectively, PLA2R1 and RASSF9 are two key genes in thyroid cancer, which have potential diagnostic, prognostic, and anti-tumor effects in thyroid cancer.
甲状腺癌是一种全球发病率不断上升的常见恶性肿瘤。本研究的目的是探索甲状腺癌中的关键基因。根据基因表达综合数据库（GEO）数据集分析差异表达基因。通过UALCAN和人类蛋白质图谱数据库确认磷脂酶A2受体1（PLA2R1）和RAS相关结构域家族成员9（RASSF9）的水平。通过基因表达谱交互分析（GEPIA）分析无病生存期和线性相关性。根据癌症基因组图谱（TCGA）数据库生成ROC曲线。使用基因集细胞分析（GSCA）平台分析甲基化水平和免疫浸润。通过蛋白质免疫印迹法检测PLA2R1、RASSF9和Wnt/β-连环蛋白相关蛋白水平。通过5-乙炔基-2'-脱氧尿苷检测评估细胞增殖。通过Transwell检测评估细胞侵袭和迁移。在来自GSE104005、GSE65144和GSE53157数据集的甲状腺癌中有2个常见的差异表达基因（PLA2R1和RASSF9）。PLA2R1和RASSF9表达降低与晚期阶段和较低的无病生存期相关。与正常样本相比，甲状腺癌样本中PLA2R1和RASSF9甲基化水平升高。PLA2R1甲基化水平与其mRNA水平呈负相关。PLA2R1和RASSF9与甲状腺癌中的免疫浸润有关。PLA2R1和RASSF9表达与放射性碘抵抗相关，且与碘摄取相关因子的表达呈正相关。PLA2R1和RASSF9的作用机制涉及多个信号通路，包括Wnt/β-连环蛋白信号通路。PLA2R1和RASSF9的过表达抑制甲状腺癌细胞中Wnt/β-连环蛋白通路的激活、增殖、侵袭和迁移。总体而言，PLA2R1和RASSF9是甲状腺癌中的两个关键基因，在甲状腺癌中具有潜在的诊断、预后和抗肿瘤作用。
