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非小细胞肺癌中卵巢肿瘤泛素异肽酶1与程序性死亡受体-1配体的表达相关性

Correlation between expression of ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 and programmed cell death-ligand 1 in non-small cell lung cancer

    摘要
  • 摘要:
    目的 探讨非小细胞肺癌（NSCLC）中卵巢肿瘤泛素异肽酶1（OTUB1）与程序性死亡受体-1配体（PD-L1）的相关性。
    方法 分析肿瘤基因组数据库（TCGA）中NSCLC与癌旁正常组织OTUB1 mRNA的差异性。基于基因表达谱数据动态分析（GEPIA）探讨NSCLC中OTUB1与PD-L1 mRNA表达相关性。免疫组化法检测46例NSCLC及41例癌旁正常组织蜡块OTUB1及PD-L1蛋白表达，收集临床病例数据及随访资料。分析OTUB1在癌组织与癌旁组织中的表达差异，OTUB1与PD-L1相关性、临床病理特征的关系以及无复发生存期（RFS）预测意义。
    结果 NSCLC与癌旁正常组织的OTUB1 mRNA及蛋白表达差异均有统计学意义（P < 0.05）。NSCLC的OTUB1与PD-L1 mRNA无相关性（P>0.05），但两者蛋白表达有相关性（P=0.029）。OTUB1与TNM分期有相关性（P=0.039），与年龄、吸烟史、分化程度、转移淋巴结数及病理类型无相关性（P>0.05）。Kaplan-Meier分析显示，TNM分期（P < 0.001）、转移淋巴结数（P=0.001）及分化程度（P=0.042）是RFS的影响因素；OTUB1阴性及阳性中位RFS分别是18、19个月，差异无统计学意义（P>0.05）。COX多因素分析结果提示，分化程度（P=0.005）及TNM分期（P=0.006）是影响RFS的独立危险因素。
    结论 NSCLC中OTUB1 mRNA及蛋白表达均高于癌旁正常组织。在蛋白水平方面，OTUB1与PD-L1呈正相关。OTUB1表达与TNM分期相关。

     

    Abstract:
    Objective To explore the correlation between ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1) and programmed cell death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC).
    Methods Differences of OTUB1 mRNA between NSCLC and corresponding non-tumor normal tissues in the Cancer Genome Atlas (TCGA) were analyzed. The correlation on mRNA expression between OTUB1 and PD-L1 in NSCLC in Gene Expression Profiling Interactive Analysis (GEPIA) was discussed. The protein expressions of OTUB1 and PD-L1 in 46 cases of NSCLC and 41 cases of corresponding non-tumor normal tissues were detected by immunohistochemistry, and the clinical case data and follow-up data were collected. The expression difference of OTUB1 between cancer tissues and adjacent tissues, the correlations between OTUB1 and PD-L1 as well as clinicopathological features, and the predictive significance for recurrence free survival (RFS) were analyzed.
    Results There were significant differences in mRNA and protein expressions of OTUB1 between NSCLC and corresponding non-tumor normal tissues (P < 0.05). There was no correlation in mRNA expression between OTUB1 and PD-L1 in NSCLC tissues (P>0.05), but there was a correlation in protein expression between OTUB1 and PD-L1 (P=0.029). OTUB1 was correlated with TNM staging (P=0.039), but had no correlation with age, history of smoking, degree of differentiation, number of metastatic lymph nodes and pathological type (P>0.05). Kaplan-Meier analysis showed that TNM staging (P < 0.001), the number of metastatic lymph nodes (P=0.001) and the degree of differentiation (P=0.042)were the influencing factors of RFS. The median RFS of negative and positive OTUB1 were 18 months and 19 months, respectively, and there was no significant difference (P>0.05). COX multivariate analysis showed that the degree of differentiation (P=0.005) and TNM staging (P=0.006) were the independent risk factors for RFS.
    Conclusion The mRNA and protein expression levels of OTUB1 in NSCLC tissue are higher than those in corresponding non-tumor normal tissues. In terms of protein level, OTUB1 is positively correlated with PD-L1. OTUB1 expression is related to TNM staging.

     

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