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

Abstract

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.

Figure 1

The relative level of cav-1 mRNA in 136 lung TT and TF samples (P<0.05).

Figure 2

Western blot analysis of the protein level of cav-1 in TT and the paired TF form 4 representative NSCLC cases. β-actin was used to normalize for any differences in protein loading between lanes. The column of the histogram represents the relative level of the cav-1 protein.

Figure 3

IHC of cav-1 protein expression in lung TT. (A) The positive immunoreactivity of cav-1 was localized in the membrane and the intracytoplasm of the lung AC. (B) The positive immunoreactivity of cav-1 was localized in fibroblasts. (C) Bronchial epithelium and smooth muscle cells showed positive staining for cav-1. (D) Negative expression of cav-1 in lung AC.

Figure 4

Survival analysis stratified by the status of the cav-1 protein expression and histological types. (A) Patients whose tumors had high cav-1 protein expression showed shorter overall survival than patients whose tumors had lower cav-1 protein expression, but the result was not statistically significant (P=0.342; log-rank test), (B) In all lung AC patients with higher cav-1 expression, significantly shorter OS was found when compared with those that had lower cav-1 expression levels (P=0.032; log-rank test).

Figure 4

Survival analysis stratified by the status of the cav-1 protein expression and histological types. (A) Patients whose tumors had high cav-1 protein expression showed shorter overall survival than patients whose tumors had lower cav-1 protein expression, but the result was not statistically significant (P=0.342; log-rank test), (B) In all lung AC patients with higher cav-1 expression, significantly shorter OS was found when compared with those that had lower cav-1 expression levels (P=0.032; log-rank test).