LOXL1和LOXL2基因在恶性胸膜间皮瘤中的表达及临床意义

Expression and clinical significance of LOXL1 and LOXL2 genes in malignant pleural mesothelioma

目的 赖氨酰氧化酶样蛋白1(LOXL1)和赖氨酰氧化酶样蛋白2(LOXL2)在恶性胸膜间皮瘤(MPM)的表达差异及其预后价值尚不明确。文中旨在探讨LOXL1和LOXL2基因mRNA在MPM组织中的表达及其临床意义。方法 回顾性收集2017年6月至2019年12月大理大学第一附属医院胸外科12例MPM患者的癌组织和配对相邻正常胸膜组织。采用RT-qPCR检测MPM组织及配对正常胸膜组织中LOXL1和LOXL2基因mRNA表达量。通过Oncomine数据库对非瘤组织与MPM组织中LOXL1和LOXL2基因的表达差异进行分析。通过R4.0.2软件对TCGA数据库中LOXL1和LOXL2基因mRNA表达量与MPM临床病理特征的相关性进行分析。构建Kaplan-Meier模型分别探讨LOXL1和LOXL2基因mRNA表达量对MPM患者预后的影响。采用基因表达谱动态分析(GEPIA)分别对LOXL1和LOXL2与MPM肿瘤标志物基因和LOX家族其他成员基因表达的相关性进行分析。结果 RT-qPCR检测显示,与正常胸膜组织比较,MPM组织中LOXL1和LOXL2基因mRNA的表达量显著增加(P<0.01)。LOXL1基因和LOXL2基因的高表达是导致MPM患者预后不良的影响因素,上皮样型MPM预示着MPM患者预后良好(P<0.05)。LOXL1基因表达与EFEMP1(r=-0.25,P=0.021)、MSLN(r=-0.35,P<0.001)、CALB2(r=-0.36,P<0.001)、THBS2(r=0.32,P=0.003)和CDH11基因(r=0.25,P=0.018)表达具有显著相关性。LOXL1基因表达与LOXL2(r=0.22,P=0.041)、LOXL4(r=0.3,P=0.004)基因具有显著正相关;LOXL2基因表达与LOX(r=0.65,P<0.001)、LOXL1(r=0.22,P=0.041)和LOXL4(r=0.37,P<0.001)基因表达具有显著正相关。结论 LOXL1和LOXL2基因在MPM组织中均呈现显著高表达,其基因表达量是评估MPM患者预后的有效指标。

Objective The difference in expression and prognostic value of llysyl oxidase-like protein 1(LOXL1) and Llysyl oxidase-like protein 2(LOXL2) in malignant pleural mesothelioma(MPM) remains unclear. The objective of this study was to investigate the expression of LOXL1 and LOXL2 mRNA in MPM and its clinical significance. Methods Cancer tissues and paired adjacent normal pleural tissues from 12 patients with MPM in the Department of Thoracic Surgery of the First Affiliated Hospital of Dali University from June 2017 to December 2019 were collected. The mRNA expression levels of LOXL1 and LOXL2 in MPM and normal pleural tissues were detected by RT-qPCR. The expression differences of LOXL1 and LOXL2 genes between non-tumor tissues and MPM tissues were analyzed by Oncomine database. The correlation between the mRNA expression levels of LOXL1 and LOXL2 in TCGA database and the clinicopathological features of MPM was analyzed by R4.02 software. The effects of LOXL1 and LOXL2 mRNA expression on the prognosis of MPM patients were investigated by Kaplan Meier model. Gene expression profile dynamic analysis(GEPIA) was used to analyze the correlation between LOXL1 and LOXL2 and the expression of MPM tumor marker genes and other members of LOX family. Results RT-qPCR showed that the mRNA expression levels of LOXL1 and LOXL2 were significantly increased in MPM compared with normal pleural tissue(P<0.01). High expression of LOXL1 gene and LOXL2 gene is a contributing factor to poor prognosis in MPM patients, and epithelioid MPM predicts a good prognosis in MPM patients(P<0.05). LOXL1 gene expression and EFEMP1(r=0.25, P=0.021), MSLN(r=0.35, P<0.001), CALB2(r=0.36, P<0.001), THBS2(r=0.32, P=0.003) and CDH11 gene expression(r=0.25, P=0.018) were significantly correlated. LOXL1 gene expression was positively correlated with LOXL2(r=0.22, P=0.041) and LOXL4(r= 0.3, P=0.004). LOXL2 gene expression was positively correlated with LOX(r=0.65, P<0.001), LOXL1(r=0.22, P=0.041) and LOXL4(r= 0.37, P<0.001). Conclusion Both LOXL1 and LOXL2 genes were significantly overexpressed in MPM tissues, and their gene expression level is an effective indicator to evaluate the prognosis of MPM patients.