摘要
目的:脊索瘤是一种较为罕见的恶性肿瘤,脊索瘤患者具有复发率高和预后差的特点。本研究旨在探讨死亡结构域相关蛋白(death domain-associated protein,DAXX)在脊索瘤中的表达及其与脊索瘤生物学行为的相关性和临床意义。方法:收集2016年1月至2022年1月手术切除的脊索瘤标本156例,其中144例有完整随访记录,12例失随访,另收集18例脊索瘤瘤旁标本。采用苏木精-伊红染色和免疫组织化学染色分析144例脊索瘤组织及18例瘤旁组织中DAXX的表达情况,并统计DAXX表达水平与各临床病理参数之间的关系,以及DAXX阳性表达患者的预后情况。在人脊索瘤细胞系(U-CH1、MUG-Chor1)中敲低DAXX表达后,使用蛋白质免疫印迹和定量聚合酶链反应(quantitative polymerase chain reaction,qPCR)分析DAXX的表达,四甲基偶氮唑盐[3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide,MTT]实验和克隆形成实验评估其对脊索瘤细胞增殖能力的影响,划痕试验和Transwell实验分析其对脊索瘤细胞侵袭和迁移能力的影响。结果:脊索瘤组织DAXX高表达91例(63.2%),低表达53例(36.8%),瘤旁组织18例(100%)均为低表达;DAXX的表达与肿瘤原发/复发及肿瘤大小均相关(均P<0.05),而与其他临床特征无关。Log-rank检验显示DAXX高表达患者的PFS和OS均显著低于DAXX低表达患者(均P<0.05)。Cox回归分析提示DAXX表达水平、肿瘤原发/复发、手术方式及肿瘤大小是术后进展的独立危险因素(均P<0.05)。在脊索瘤细胞中敲低DAXX表达后,细胞的增殖、侵袭和迁移均显著抑制(均P<0.001)。结论:脊索瘤中DAXX的高表达与不良预后密切相关,在脊索瘤细胞中敲低DAXX表达可降低肿瘤侵袭能力。因此,DAXX有望成为判断脊索瘤患者肿瘤进展和预后的预测因子。
Objective:Chordoma is a rare malignant tumor characterized by a high recurrence rate and poor prognosis.This study aims to investigate the expression of death domain-associated protein(DAXX)in chordoma and its correlation with tumor biological behavior and clinical significance.Methods:A total of 156 chordoma specimens surgically resected between January 2016 and January 2022 were collected,among which 144 cases had complete follow-up data and 12 were lost to follow-up.In addition,18 adjacent non-tumor tissue samples were included.Hematoxylin-eosin and immunohistochemical staining were performed to analyze DAXX expression in 144 chordoma tissues and 18 adjacent tissues.The relationship between DAXX expression and clinicopathological parameters was examined,and the prognostic outcomes of DAXX-positive patients were evaluated.In chordoma cell lines(U-CH1,MUG-Chor1),DAXX knockdown was achieved,followed by western blotting and quantitative polymerase chain reaction(qPCR)to assess DAXX expression.The effects on cell proliferation were evaluated by MTT and colony formation assays,while migration and invasion were assessed by wound healing and Transwell assays.Results:High DAXX expression was observed in 91 cases(63.2%)of chordoma and low expression in 53 cases(36.8%);all 18 adjacent tissues showed low expression.DAXX expression was correlated with primary/relapsed tumor status and tumor size(both P<0.05),but not with other clinical features.Log-rank test analysis revealed that patients with high DAXX expression had significantly lower progression-free survival(PFS)and overall survival(OS)compared with those with low DAXX expression(both P<0.05).Cox regression analysis identified DAXX expression level,tumor primary/relapse status,surgical method,and tumor size as independent risk factors for postoperative progression(all P<0.05).In vitro,DAXX knockdown significantly suppressed chordoma cell proliferation,invasion,and migration(all P<0.001).Conclusion:High DAXX expression in chordoma is closely associated with poor prognosis,while DAXX knockdown inhibits tumor aggressiveness.DAXX may serve as a predictive marker for tumor progression and prognosis in chordoma patients.
作者
姚正奇
陈素
矫健
杨明磊
钟南哲
肖建如
YAO Zhengqi;CHEN Su;JIAO Jian;YANG Minglei;ZHONG Nanzhe;XIAO Jianru(School of Health Sciences and Engineering,University of Shanghai for Science and Technology,Shanghai 200433;Department of Orthopaedics,Changzheng Hospital Second Military Medical University,Shanghai 200433,China)
出处
《临床与病理杂志》
2025年第5期527-538,共12页
Journal of Clinical and Pathological Research
基金
国家自然科学基金(81902731
82173028)。
关键词
死亡结构域相关蛋白
脊索瘤
预后
生物学行为
免疫组织化学染色
death domain-associated protein
chordoma
prognosis
biological behavior
immunohistochemical staining
