Background
To investigate the relationship between CXCR4-related circular RNAs (circRNAs) in exosomes and lymph node metastasis of lung adenocarcinoma.
Conclusions
Taken together, our findings suggested that CXCR4 was higher in the lung adenocarcinoma tissues with lymph node metastasis. Higher plasma levels of exo-hsa_circRNA_0056616 in these patients also suggest that this circRNA represents a potential biomarker for lymph node metastasis predictor in lung adenocarcinoma.
Methods
Totally 41 lung adenocarcinoma tissues (21 with lymph node metastasis and 20 without) were collected. Expression of CXCR4 protein was detected by western blotting analysis. A stable PC9/CXCR4-shRNA and PC14/CXCR4-shRNA knockdown lung adenocarcinoma cell lines were established and subjected to functional assays (cell proliferation, colony formation, migration and invasion) for phenotype changes. Exo-hsa-circRNAs (has-circRNAs in exosomes) were detected in vivo and in vitro. The diagnostic value of differentially expressed exo-has-circRNAs was evaluated.
Results
Expression levels of CXCR4 were higher in patients with lymph node metastasis than in those without (P = 0.001). Silencing CXCR4 expression in PC9 and PC14 cell lines with short hairpin RNA could effectively abolish colony formation frequency, proliferation rate, migration rate, and the number of invasive cells (all P < 0.001). Exo_circRNA_0056616 was detected in both PC-9/CXCR4-shRNA cells and lung adenocarcinoma plasma at significantly higher levels than in the corresponding control (P < 0.001). When a receiver operating characteristic (ROC) curve for plasma exo-hsa_circRNA_0056616 levels and diagnosis of lymph node metastasis of lung adenocarcinoma was generated, a cutoff value of 0.394 was identified with an area under the curve of 0.812 (95% confidence interval 0.720-0.903), a sensitivity of 0.792, and specificity of 0.810. Conclusions: Taken together, our findings suggested that CXCR4 was higher in the lung adenocarcinoma tissues with lymph node metastasis. Higher plasma levels of exo-hsa_circRNA_0056616 in these patients also suggest that this circRNA represents a potential biomarker for lymph node metastasis predictor in lung adenocarcinoma.