Abstract
BackgroundCaveolin-1 (Cav-1) plays an important role in the development of various human cancers. We investigated the relationship between Cav-1 expression and non-small cell lung cancer (NSCLC) progression in the context of brain metastasis (BM).MethodsCav-1 expression was investigated in a series of 102 BM samples and 49 paired primary NSCLC samples, as well as 162 unpaired primary NSCLC samples with (63 cases) or without (99 cases) metastasis to distant organs. Human lung cancer cell lines were used for in vitro functional analysis.ResultsHigh Cav-1 expression in tumor cells was observed in 52% (38/73) of squamous cell carcinomas (SQCs) and 33% (45/138) of non-SQCs. In SQC, high Cav-1 expression was increased after BM in both paired and unpaired samples of lung primary tumors and BM (53% vs. 84% in paired samples, P = 0.034; 52% vs. 78% in unpaired samples, P = 0.020). Although the difference in median overall survival in patients NSCLC was not statistically significant, high Cav-1 expression in tumor cells (P = 0.005, hazard ratio 1.715, 95% confidence index 1.175–2.502) was independent prognostic factors of overall survival on multivariate Cox regression analyses, in addition to the presence of BM and non-SQC type. In vitro assays revealed that Cav-1 knockdown inhibited the invasion and migration of lung cancer cells. Genetic modulation of Cav-1 was consistently associated with SNAIL up- and down-regulation. These findings were supported by increased SNAIL and Cav-1 expression in BM samples of SQC.ConclusionsCav-1 plays an important role in the BM of NSCLC, especially in SQC. The mechanism may be linked to SNAIL regulation.
Highlights
Caveolin-1 (Cav-1) plays an important role in the development of various human cancers
Human tissue specimens and clinical data From January 1, 2007 to December 31, 2012, 105 cases affected by brain metastasis (BM) originating from non-small cell lung cancer (NSCLC) were enrolled
Group 1 comprised BM cases originating from NSCLC, Group 2 comprised primary NSCLC cases paired to the Group 1 cases, Group 3 comprised primary NSCLC cases without any systemic metastasis, and Group 4 comprised primary NSCLC cases with distant metastasis to organs other than the brain
Summary
Caveolin-1 (Cav-1) plays an important role in the development of various human cancers. We investi‐ gated the relationship between Cav-1 expression and non-small cell lung cancer (NSCLC) progression in the context of brain metastasis (BM). Lung cancers are classified into several types based on the histologic classification. Non-small cell lung cancer (NSCLC), represented by adenocarcinoma (ADC) and squamous cell carcinoma (SQC), presents distinguished clinical courses with differences in treatment planning and prognosis prediction, compared to small cell lung cancer (SCLC) [2]. With the incidence of histologic subtype, ADC is the most common type, followed by SQC, and SCLC [3]. Brain metastasis (BM) develops in approximately 40% of patients with NSCLC and generally results in a dismal prognosis [4,5,6]. A deeper understanding of the molecular pathogenesis underlying BM of NSCLC is essential for improving patient prognosis
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