Department of General Surgery, The Second Clinical Medical College, Lanzhou University, Lanzhou, 730030 Gansu, China.
Department of Head & Neck Oncology Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310022 Zhejiang, China.
Dis Markers. 2022 Jun 20;2022:1606404. doi: 10.1155/2022/1606404. eCollection 2022.
Thyroid cancer (THCA) represents a frequently seen endocrine cancer, which can be divided as anaplastic thyroid carcinoma (ATC), follicular thyroid carcinoma (FTC), and papillary thyroid carcinoma (PTC). A total of 362 IDEGs were obtained from TCGA-THCA and IMMPORT databases, which were found to be related to BP, CC, MF, and STAT signaling pathway upon GO functional annotation and KEGG analysis. This work identified 23 survival-related hub genes using WGCNA and uniCOX analysis. In addition, a risk prognosis model was constructed to obtain a signature involving fifteen IDEGs. According to survival and univariate along with multivariate analysis, high-risk patients had markedly dismal prognostic outcome compared with low-risk counterparts. Siglec-15 belongs to one of the fifteen IDEG signature, but the precise biological roles in diverse THCA subtypes are largely unclear. In this work, Siglec-15 expression evidently increased in ATC and FTC samples compared with matched surrounding PTC and THCA samples, which was used as a diagnostic biomarker for THCA. Siglec-15 RNAi significantly inhibited cell proliferation and promoted cell apoptosis. Meanwhile, Siglec-15 knockout suppressed the expression of STAT1, STAT3, and VEGF and promoted that of cleaved caspase-3. In experiments revealed that transfection with vectors expressing STAT1 and STAT3 inhibited the Siglec-15 RNAi-induced inhibition on tumor growth and the increases in CD4/CD8 ratio. In conclusion, Siglec-15 expression increases in ATC and FTC, which promotes THCA occurrence via the STAT1/STAT3 signaling, in particular for FTC and ATC. Therefore, it is the possible marker that can be used to diagnose and treat THCA.
甲状腺癌 (THCA) 是一种常见的内分泌癌，可分为间变性甲状腺癌 (ATC)、滤泡性甲状腺癌 (FTC) 和乳头状甲状腺癌 (PTC)。从 TCGA-THCA 和 IMMPORT 数据库中获得了总共 362 个 IDEGs，通过 GO 功能注释和 KEGG 分析发现它们与 BP、CC、MF 和 STAT 信号通路有关。本研究通过 WGCNA 和 uniCOX 分析确定了 23 个与生存相关的枢纽基因。此外，构建了一个风险预后模型，获得了一个包含 15 个 IDEG 的特征。根据生存和单因素以及多因素分析，高危患者的预后明显差于低危患者。Siglec-15 属于 15 个 IDEG 特征之一，但在不同 THCA 亚型中的精确生物学作用尚不清楚。在这项研究中，Siglec-15 在 ATC 和 FTC 样本中的表达明显高于匹配的周围 PTC 和 THCA 样本，可作为 THCA 的诊断生物标志物。Siglec-15 RNAi 显著抑制细胞增殖并促进细胞凋亡。同时，Siglec-15 敲除抑制了 STAT1、STAT3 和 VEGF 的表达，促进了 cleaved caspase-3 的表达。实验表明，转染表达 STAT1 和 STAT3 的载体抑制了 Siglec-15 RNAi 对肿瘤生长的抑制作用和 CD4/CD8 比值的增加。总之，Siglec-15 在 ATC 和 FTC 中的表达增加，通过 STAT1/STAT3 信号促进 THCA 的发生，特别是对 FTC 和 ATC。因此，它可能是一种用于诊断和治疗 THCA 的标志物。
