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基于生物信息学探讨赖氨酸氧化酶在食管癌原发灶中的表达及对骨转移患者预后的影响

Expression of lysine oxidase in primary lesion of esophageal cancer and its effect on prognosis of patients with bone metastases based on bioinformatics

    摘要
  • 摘要:
    目的 基于生物信息学探讨赖氨酸氧化酶(Lox)在食管癌(ESCA)原发灶及骨转移灶中的表达及临床意义。
    方法 通过癌症基因组图谱(TCGA)及基因表达谱分析互动平台(GEPIA)数据库筛选ESCA与正常食管组织中差异表达的基因。筛选2016年1月—2020年12月河北医科大学第四医院收治的食管癌手术患者的随访信息, 收集在随访过程中确诊骨转移患者的临床资料。应用蛋白免疫印迹(Western blot)验证Lox在ESCA及正常食管组织中的表达; 通过免疫组化染色检测人ESCA组织、正常组织中Lox的表达; 应用Kaplan-Meier曲线及Cox回归探索Lox的表达对于生存期的影响。
    结果 对GEPIA及TCGA数据库有关ESCA数据分析发现, Lox在ESCA病灶中的表达高于正常组织，差异有统计学意义(P<0.05); 应用京都基因与基因组百科全书(KEGG)及基因富集分析(GO)发现, Lox可能参与多种信号通路的信息传导; Western blot结果显示，癌组织中Lox表达高于癌旁正常组织，差异有统计学意义(P<0.05); 对随访资料的分析发现, Lox高表达患者更倾向于发生多发骨转移; 生存分析发现Lox高表达患者无骨转移生存期和总生存期短于Lox低表达的患者，差异有统计学意义(P<0.05); Cox回归发现Lox是食管癌骨转移患者预后的独立危险因素。
    结论 Lox在ESCA中呈高表达，并与临床预后相关，其可作为ESCA诊断及治疗的有效靶点。

     

    Abstract:
    Objective To explore the expression and clinical significance of lysine oxidase (Lox) in primary lesion of esophageal carcinoma (ESCA) and bone metastasis lesion based on bioinformatics.
    Methods The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to screen for differentially expressed genes between ESCA and normal esophageal tissues. Follow-up information of patients with surgery for esophageal cancer in the Fourth Hospital of Hebei Medical University from January 2016 to December 2020 were screened, and the clinical materials of patients diagnosed as bone metastasis during the follow-up period were collected. Western blot was used to verify the expression of Lox in ESCA and normal esophageal tissues; immunohistochemical staining was used to detect the expression of Lox in human ESCA tissue and normal tissue; the impact of Lox expression on survival was explored by Kaplan-Meier curve and Cox regression.
    Results Through the analysis of ESCA data in GEPIA and TCGA databases, it was found that the expression of Lox in ESCA lesions was significantly higher than that in normal tissues (P<0.05); the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses found that Lox may be involved in the information conduction of various signaling pathways; the Western blot result showed that the expression of Lox in cancer tissue was higher than that in adjacent normal tissue (P<0.05); the analysis of follow-up data found that patients with high expression of Lox were more likely to have multiple bone metastases; survival analysis revealed that patients with high Lox expression had significantly shorter bone metastasis free survival and overall survival compared to patients with low Lox expression (P<0.05); Cox regression found that Lox was an independent risk factor for prognosis of patients with esophageal cancer bone metastasis.
    Conclusion Lox is highly expressed in ESCA and significantly related to clinical prognosis, which can be used as an effective target for the diagnosis and treatment of ESCA.

     

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