Abstract
Purpose
Caveolin is an essential constituent of caveolae and has many biological functions. Expression of caveolin-1 in cancer cells was reported to be a prognostic marker in several types of cancers, the prognostic significance of its expression in cancer-associated fibroblasts (CAFs) has not been investigated. This study aimed to evaluate the clinicopathological significance of expression by CAFs in lung adenocarcinoma.
Methods
We examined caveolin-1 expression in both CAFs and cancer cells in stage I invasive lung adenocarcinoma (n = 412) and analyzed the relationship between the expression and clinicopathological factors.
Results
Caveolin-1 expression by CAFs and cancer cells was observed in 12.1% and 7.8% of adenocarcinomas, respectively. Tumors with caveolin-1-positive CAFs had vascular and pleural invasion significantly more frequently than those with caveolin-1-negative CAF (p < 0.05). This was also the cases with tumors with caveolin-1-positive cancer cells (p < 0.01). Caveolin-1 expression by CAFs and that by cancer cells were significant predictors of shorter recurrence-free survival (p < 0.001). Caveolin-1 expression by CAFs and cancer cells was found in 25% and 30% of solid predominant subtype, respectively, but only 9.2% and 2.7% of non-solid predominant subtype, respectively. The frequency of cases with caveolin-1-positive CAFs or cancer cells was significantly higher in the solid predominant subtype than in non-solid predominant subtype (p < 0.001).
Conclusions
Our current results highlight the prognostic importance of caveolin-1 expression by CAFs in stage I lung adenocarcinoma and provide new insights into the biological significance of caveolin-1 in the tumor microenvironment, especially in microenvironment of solid predominant adenocarcinoma.
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Acknowledgments
This work was supported by the National Cancer Center Research and Development Fund (26-A-16), the Foundation for the Promotion of Cancer Research, the 3rd Term Comprehensive 10-Year Strategy for Cancer Control, the Advanced Research for Medical Products Mining Programme of the National Institute of Biomedical Innovation (NIBIO).
Authors’ contribution
KS and GI conceived the study. KS and KK carried out the experiments. KS and GI analyzed the data. KS and GI were involved in writing the paper. All authors had final approval of the manuscript.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Shimizu, K., Kirita, K., Aokage, K. et al. Clinicopathological significance of caveolin-1 expression by cancer-associated fibroblasts in lung adenocarcinoma. J Cancer Res Clin Oncol 143, 321–328 (2017). https://doi.org/10.1007/s00432-016-2285-2
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DOI: https://doi.org/10.1007/s00432-016-2285-2