探讨甲状腺乳头状癌（PTC）中SF3B5的表达及其与PTC患者的临床病理特征的相关性，并揭示SF3B5在PTC进展中的功能及分子机制。

分析癌症基因组图谱（TCGA）数据库中PTC以及正常组织SF3B5的表达水平及其与临床病理特征及预后的相关性。采用单纯随机抽样法，回顾性收集2011年1月至2015年6月的95例PTC患者资料，采用免疫组织化学染色检测PTC患者组织SF3B5的表达，采用卡方检验、单因素及多因素Logistic回归分析探讨SF3B5与PTC临床病理特征的相关性。构建过表达SF3B5的TPC-1、KTC-1细胞系，进行细胞表型实验，探究SF3B5对细胞增殖、迁移能力的影响，同时提取总RNA进行转录物组测序，对测序数据及TCGA数据库进行基因本体论（GO）、京都基因和基因组数据库（KEGG）分析、基因集富集分析（GSEA），并通过蛋白质印迹法（Western blotting）验证下游通路分子。

（1）TCGA数据库分析显示，SF3B5在PTC组织中的表达水平低于邻近正常组织；SF3B5在BRAF突变、腺外侵犯、侧颈淋巴结转移（LLNM）、T3/T4、R1/R2的PTC组织中表达显著下调（P<0.05）。（2）免疫组织化学染色分析提示，在PTC组织中SF3B5低表达50例，高表达45例，与SF3B5高表达患者相比，SF3B5低表达患者中有LLNM的比例显著升高（P=0.043）。（3）SF3B5低表达、腺外侵犯是影响PTC患者LLNM的独立危险因素。（4）SF3B5通过JAK-STAT、TGF-β信号通路抑制PTC的进展。

SF3B5在PTC中表达下调，其低表达是PTC患者LLNM的独立危险因素。SF3B5通过调控JAK-STAT及TGF-β信号通路抑制肿瘤进展。SF3B5有望成为评估PTC转移风险的新型分子标志物及潜在治疗靶点。

To investigate the expression of SF3B5 in papillary thyroid carcinoma (PTC) and its correlation with clinicopathological characteristics of PTC patients, and to reveal the function and molecular mechanisms of SF3B5 in PTC progression.

The expression levels of SF3B5 in PTC and normal tissues from the The Cancer Genome Atlas (TCGA) database were analyzed for their correlation with clinicopathological features and prognosis. A retrospective study was conducted on 95 patients with PTC selected by simple random sampling from January 2011 to June 2015. Clinicopathological data were collected, and SF3B5 expression in PTC tissues was detected by immunohistochemical staining. The Chi-square test, univariate, and multivariate Logistic regression analyses were used to explore the correlation between SF3B5 and PTC clinicopathological characteristics. TPC-1 and KTC-1 cell lines with overexpressing SF3B5 were constructed for cell phenotype experiments to investigate the effects of SF3B5 on cell proliferation and migration. Total RNA was extracted for transcriptome sequencing. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) enrichment analyses were performed on the transcriptome sequencing data and TCGA database data. Downstream pathway molecules were validated by Western blotting.

(1) TCGA database analysis showed that SF3B5 expression was lower in PTC tissues compared to adjacent normal tissues. SF3B5 expression was significantly decreased in PTC tissues with BRAF mutation, extrathyroidal extension, lateral lymph node metastasis (LLNM), T3/T4 stage, and R1/R2 resection status (P<0.05). (2) Immunohistochemical staining analysis revealed low SF3B5 expression in 50 cases and high expression in 45 cases among PTC tissues. Compared to patients with high SF3B5 expression, the proportion of patients with LLNM was significantly higher in the low SF3B5 expression group (P=0.043). (3) Low SF3B5 expression and extrathyroidal extension were independent risk factors affecting LLNM in PTC patients. (4) SF3B5 inhibited PTC progression through the JAK-STAT and TGF-β signaling pathways.

SF3B5 is downregulated in PTC, and its low expression serves as an independent risk factor for lateral lymph node metastasis in PTC patients. Mechanistically, SF3B5 suppresses tumor progression through negative regulation of the JAK-STAT and TGF-β signaling pathways. These findings suggest that SF3B5 may serve as a novel biomarker for assessing metastatic risk and represent a potential therapeutic target in PTC.