河北医科大学学报 ›› 2025, Vol. 46 ›› Issue (4): 465-473.doi: 10.3969/j.issn.1007-3205.2025.04.015

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BST2在喉鳞状细胞癌中的表达特征及其意义

  

  1. 河北医科大学第二医院耳鼻喉一科,河北 石家庄 050000

  • 出版日期:2025-04-25 发布日期:2025-04-17
  • 作者简介:杨钰玮(1997-),女,河北衡水人,河北医科大学第二医院医师,医学硕士,从事耳鼻喉科疾病诊治研究。

  • 基金资助:
    河北省自然科学基金(H2020206475);河北省重点研发计划项目民生科技专项(20372401D);河北省医学科学研究课题计划(20210408)

Expression characteristics and significance of BST2 in laryngeal squamous cell carcinoma

  1. Department of Otolaryngology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China

  • Online:2025-04-25 Published:2025-04-17

摘要: 目的 探讨骨髓基质细胞抗原2(bone marrow stromal cell antigen 2,BST2)基因在人喉鳞状细胞癌组织中的表达特征及与患者预后及病理特征的关系,明确BST2基因沉默对喉癌细胞系细胞增殖、细胞侵袭、细胞迁移的影响。
方法 通过免疫组织化学实验方法检测BST2在喉癌组织和癌旁组织中的差异表达。采用(cell counting kit 8,CCK-8)法检测BST2基因沉默后对细胞增殖状况的影响,细胞划痕实验检测BST2基因沉默后对细胞迁移能力的影响,Transwell实验检测BST2基因沉默后对细胞侵袭能力的影响。收集患者的临床资料,分析临床参数与BST2蛋白表达水平之间的相关性。Kaplan-Meier生存曲线比较不同BST2蛋白的表达患者的生存时间,采用单因素分析和多因素Cox回归分析患者临床特征对生存时间的影响,受试者工作特征(receiver operating characteristic,ROC)曲线分析评价BST2的预测价值。
结果 免疫组织化学结果显示,BST2蛋白在喉癌组织中的表达高于癌旁组织,差异有统计学意义(P<0.001)。在TU686细胞系中,CCK-8结果表明,48 h后siRNA-3组的OD值为2.35±0.18,显著低于正常对照组2.87±0.13和阴性对照组2.71±0.12(F=16.330,P<0.001)。细胞划痕实验表明,12 h后BST2基因沉默组细胞愈合率为(15.1±3.71)%,显著低于正常对照组(35.07±5.25)%和阴性对照组(33.03±5.04)%(F=16.280,P=0.004);24 h后BST2基因沉默组细胞愈合率为(30.41±4.01)%,显著低于正常对照组(75.05±4.44)%和阴性对照组(70.6±4.97)%(F=89.951,P<0.001)。Tanswell实验表明,BST2基因沉默组细胞侵袭的细胞数为82.67±2.51,显著低于正常对照组134.67±2.52和阴性对照组121.67±4.73(F=188.314,P<0.001)。不同临床分期(P=0.032)及生存时间(P<0.001)喉癌患者BST2表达水平差异有统计学意义;Kaplan-Meier生存曲线分析显示,BST2表达水平较高的患者生存时间较短(HR=5.102,P<0.001)。单因素分析结果显示:不同临床分期(χ2=17.383,P<0.001)、淋巴结转移(χ2=14.928,P<0.001)及BST2表达水平(χ2=21.165,P<0.001)喉癌患者的生存时间差异有统计学意义;多因素Cox回归模型结果显示,临床分期(HR=4.228,95%CI:1.881~9.501,P<0.001)及BST2表达水平(HR=4.757,95%CI:2.259~10.019,P<0.001)是喉癌患者生存时间的影响因素。ROC分析显示,BST2表达水平对喉癌患者预后有较好的预测价值(曲线下面积为0.730)。
结论 BST2蛋白在喉癌组织中高表达,BST2高表达可以促进喉癌细胞的增殖、侵袭和迁移能力,且BST2高表达率与喉癌患者生存时间有关。


关键词: 喉肿瘤, 骨髓基质细胞抗原2, 生存

Abstract: Objective To investigate the expression characteristics of bone marrow stromal cell antigen 2 (BST2) gene in human laryngeal squamous cell carcinoma and its relationship with the prognosis and pathological features of patients, and to determine the effects of BST2 gene silencing on the proliferation, invasion and migration of laryngeal cancer cell lines. 
 Methods Immunohistochemistry was used to detect the differential expression of BST2 in laryngeal cancer tissues and adjacent tissues. The effects of BST2 gene silencing on cell proliferation,migration ability and invasion ability were detected by cell counting kit 8 (CCK-8) method, cell scratch test, and Transwell test, respectively. Clinical data of patients were collected to analyze the correlation between clinical parameters and the expression level of BST2 protein. Kaplan-Meier survival curve was used to compare the survival time of patients with different expressions of BST2 protein. Univariate and multivariate Cox regression analyses were used to analyze the effects of clinical characteristics on survival time of patients. The predictive value of BST2 was evaluated by receiver operating characteristic (ROC) curve. 
 Results The immunohistochemical results showed that the expression of BST2 protein in laryngeal cancer tissues was higher than that in adjacent tissues, showing significant difference (P<0.001). In the TU686 cell line, the results of CCK-8 showed that the OD value of siRNA-3 group was 2.35±0.18 at 48 h, which was significantly lower than that of the normal control group 2.87±0.13 and negative control group 2.71±0.12 (F=16.330, P<0.001). The cell scratch test showed that the healing rate of the BST2 gene silencing group was (15.1±3.71)% at 12 h, which was significantly lower than that of the normal control group (35.07±5.25)% and the negative control group (33.03±5.04)% (F=16.280, P=0.004); the healing rate was (30.41±4.01)% at 24 h, which was significantly lower than that of the normal control group (75.05±4.44)% and the negative control group (70.6±4.97)% (F=89.951, P<0.001). The Tanswell experiment showed that the number of invasive cells in the BST2 gene silencing group was 82.67±2.51, which was significantly lower than that of the normal control group 134.67±2.52 and the negative control group 121.67±4.73 (F=188.314, P<0.001).  There were significant differences in the expression of BST2 in patients with different clinical stages (P=0.032) and survival time (P<0.001). Kaplan-Meier survival curve analysis showed that higher BST2 expression level was associated with shorter survival time (HR=5.102, P<0.0001). Univariate analysis results showed that, clinical stage (χ2=17.383, P<0.001), lymph node metastasis (χ2=14.928, P<0.001) and BST2 expression level (χ2=21.165, P<0.001) were significantly correlated with the survival time of laryngeal cancer patients. The results of multivariate COX regression model showed that, clinical stage (HR=4.228, 95%CI: 1.881-9.501, P<0.001) and BST2 expression level (HR=4.757, 95%CI: 2.259-10.019, P<0.001) was influencing factors of the survival time of these patients, and ROC analysis showed that the expression level of BST2 had a good predictive value for the prognosis of the patients (AUC=0.730). 
 Conclusion BST2 protein is highly expressed in laryngeal cancer tissues, and the high expression of BST2 can promote the proliferation, invasion and migration of laryngeal cancer cells. In addition, the high expression rate of BST2 is related to the survival of laryngeal cancer patients. 


Key words: laryngeal neoplasms, bone marrow stromal cell antigen 2, survival