First Department of Respiratory Medicine, Nanjing Chest Hospital, 215 Guangzhou Road, Nanjing 210029, China.
Med Oncol. 2012 Jun;29(2):648-55. doi: 10.1007/s12032-011-9959-z. Epub 2011 Apr 26.
Lysyl oxidase-like 2 (LOXL2) belongs to an amine oxidase family whose members have been implicated in crosslink formation in stromal collagens and elastin, cell motility, and tumor development and progression. Both down- and up-regulation of LOXL in tumor tissues and cancer cell lines have been described, suggesting paradoxical roles in cancer. However, LOXL2 expression and the clinical significance in non-small cell lung cancers (NSCLC) remain unresolved. Real-time PCR was performed to detect the expression of LOXL2 mRNA in lung tumor tissues (TT) and surrounding normal tissues (sNT). Moreover, the expression of the LOXL2 protein in specimens from 83 paraffin-embedded blocks was examined by immunohistochemical staining. Correlations between LOXL2 mRNA and protein expression and clinicopathological features were evaluated by statistical analysis. In the 137 patients examined, LOXL2 mRNA expression was significantly lower in lung TT than the sNT (P < 0.05). Forty-eight specimens (48/83) showed low expression of LOXL2, as characterized by immunohistochemical staining. By statistical analysis of the correlation between LOXL2 mRNA expression and clinical features of NSCLC patients, down-regulation of Loxl-2 mRNA expression was correlated with male patients (P = 0.008), a poorer N-stage (P = 0.032) and a poorer pathological TNM stage (P = 0.003). Statistical analysis of the correlation between LOXL2 protein expression and clinical features of NSCLC patients showed a statistically significant difference between low expression of the LOXL2 protein and a poorer N-stage (P = 0.036), a higher pathological TNM stage (P = 0.005) and poorer differentiation (P = 0.035). When stratified by histological types, significant differences at both the mRNA and protein levels were only found for lung adenocarcinomas patients, and not for lung squamous cell carcinomas patients. The level of LOXL2 mRNA expression was found to be significantly down-regulated in NSCLC, and the lower mRNA and protein expression levels correlated with poorer differentiation, higher N-stage and advanced pathologic TNM stage in patients with lung adenocarcinomas.
赖氨酰氧化酶样蛋白 2（LOXL2）属于胺氧化酶家族，其成员已被牵连到基质胶原和弹性蛋白的交联形成、细胞迁移以及肿瘤的发生和发展中。在肿瘤组织和癌细胞系中，已经描述了 LOXL2 的下调和上调，这表明其在癌症中具有矛盾的作用。然而，LOXL2 在非小细胞肺癌（NSCLC）中的表达及其临床意义仍未得到解决。实时 PCR 用于检测肺肿瘤组织（TT）和周围正常组织（sNT）中 LOXL2 mRNA 的表达。此外，通过免疫组织化学染色检查了 83 个石蜡包埋块标本中 LOXL2 蛋白的表达。通过统计学分析评估 LOXL2 mRNA 和蛋白表达与临床病理特征之间的相关性。在检查的 137 例患者中，TT 中的 LOXL2 mRNA 表达明显低于 sNT（P <0.05）。48 例标本（48/83）的 LOXL2 表达较低，免疫组化染色特征为低表达。通过 NSCLC 患者 LOXL2 mRNA 表达与临床特征的相关性统计分析，Loxl-2 mRNA 表达下调与男性患者（P = 0.008）、较差的 N 期（P = 0.032）和较差的病理 TNM 期（P = 0.003）相关。NSCLC 患者 LOXL2 蛋白表达与临床特征的相关性统计分析显示，LOXL2 蛋白低表达与较差的 N 期（P = 0.036）、较高的病理 TNM 期（P = 0.005）和较差的分化（P = 0.035）之间存在统计学差异。按组织学类型分层，仅在肺腺癌患者中，在 mRNA 和蛋白水平均发现有统计学差异，而在肺鳞癌患者中无统计学差异。发现 NSCLC 中 LOXL2 mRNA 表达明显下调，较低的 mRNA 和蛋白表达水平与肺腺癌患者分化程度较差、N 期较高和病理 TNM 期较晚相关。
