【摘要】 目的 探讨跨膜丝氨酸蛋白酶14(transmembrane serine protease 14,ST14)在胶质瘤中的表达特征及与预后的相关性，并分析其与肿瘤免疫微环境的关联。方法 基于公开数据库系统分析ST14在胶质瘤中的表达特征及其与临床病理特征、预后和免疫浸润的关系，并采用Western blot检测脑组织ST14蛋白表达。在U251细胞系中敲低ST14后，采用Transwell实验检测细胞的迁移、侵袭能力；划痕愈合实验检测细胞迁移能力；CCK??8实验检测细胞增殖能力。结果 ST14在胶质瘤中高表达，其表达与异柠檬酸脱氢酶（isocitrate dehydrogenase,IDH）状态及1p/19q共缺失状态等特征相关（均P<0.05）;ST14高表达组总体生存（overall survival,OS）时间显著缩短（P<0.001）。多因素Cox回归分析显示，校正年龄、WHO分级及IDH状态等因素后，ST14仍独立影响OS(HR=1.246,95%CI:1.100～1.412,P<0.001)。基于ST14及临床特征构建的列线图可预测1、3、5年OS并进行风险分层。ST14高表达与免疫评分、免疫细胞浸润及多种免疫调节分子表达相关（均P<0.05）。结论 ST14在胶质瘤中异常高表达，敲低后可抑制U251细胞增殖、迁移和侵袭，并与不良预后及免疫微环境特征相关，有望成为胶质瘤预后评估的候选生物标志物和辅助风险分层指标。更多还原

【Abstract】 Objective To investigate the expression characteristics and prognostic correlation of transmembrane serine protease 14(ST14) in glioma, to analyze its association with the tumor immune microenvironment. Methods The expression pattern of ST14 in glioma and its associations with clinicopathological characteristics, prognosis, and immune infiltration were systematically analyzed based on public databases. Western blot was used to detect ST14 protein expression in brain tissues. After knocking down ST14 in the U251 cell line, transwell assays were used to detect cell migration and invasion ability, wound??healing assays were applied to assess cell migratory capacity, and cell counting kit??8(CCK??8) assays were conducted to quantify cell proliferation ability, so as to evaluate its effect on the malignant bio??logical behavior of glioma cells. Results ST14 was highly expressed in glioma, and its expression was associated with adverse molecular features, including isocitrate dehydrogenase(IDH) status and chromosome 1p/19q codeletion status(all P<0.05). The overall survival(OS) of the high ST14 expression group was significantly shortened(all P<0.001). Multivariate Cox regression analysis showed that ST14 remained independently associated with OS after adjustment for age, WHO grade, IDH status, and other factors(HR=1.246, 95%CI: 1.100-1.412, P<0.001). A nomogram incorporating ST14 and clinical characteristics could predict 1??, 3??, and 5??year OS and achieve risk stratification. Immune analysis showed that high ST14 expression was associated with immune scores, altered immune cell infiltration patterns, and the expression of multiple immunoregulatory molecules(all P<0.001). Conclusions ST14 is aberrantly highly expressed in glioma. Knocking down ST14 can inhibit the proliferation, migration and invasion of U251 cells, and ST14 is associated with poor prognosis and immune microenvironment characteristics,suggesting that ST14 may serve as a candidate biomarker for prognostic evaluation and an auxiliary indica??tor for risk stratification in glioma.更多还原