Down-regulation of lysyl oxidase-like 2 (LOXL2) is associated with disease progression in lung adenocarcinomas.

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.

Expression of caveolin-1 is correlated with disease stage and survival in lung adenocarcinomas.

Caveolin-1 (cav-1) has been implicated in the development of human cancers. However, the distribution of cav-1 in non-small cell lung cancer (NSCLC) and its significance require further study. Real-time PCR and Western blot assays were performed to detect cav-1 mRNA and protein levels in tumor tissues (TT) and matched tumor-free tissues (TF). The protein expression in 115 paraffin-embedded blocks was examined by immunohistochemical staining (IHC). Correlations between cav-1 mRNA and protein expression by IHC and clinicopathological features were statistically evaluated. For the 136 patients examined, the levels of cav-1 mRNA and protein expression were significantly lower in lung TT compared to matched TF (P<0.05). High cav-1 expression was detected in 60 of 115 (52.2%) NSCLC tissues and this level was significantly lower than cav-1 expression in non-cancerous lung tissues (15 of 19, 78.9%, P<0.05). Up-regulation of cav-1 mRNA expression in lung adenocarcinoma (AC) (29.7%) was higher than that observed in lung squamous cell carcinoma (SCC) (15.8%). Statistical analysis of the correlation between cav-1 protein expression and clinical features showed a statistical association with poorer N-stage (P=0.032) and higher pathological TNM stage (P=0.012) in lung AC patients, that was not found in lung SCC patients. Moreover, lung AC patients with higher cav-1 expression showed significantly shorter life-spans than those with lower cav-1 expression (P=0.032, log-rank test). The levels of cav-1 mRNA and protein expression were significantly lower in lung cancers when compared to matched TF or non-cancerous lung tissues. The higher protein expression correlated with the advanced pathological stage and shorter survival rates in lung AC patients.