Clinical utility of cerebrospinal fluid-derived circular RNAs in lung adenocarcinoma patients with brain metastases.

ABSTRACT

BACKGROUND: Free circular RNAs(circRNAs) escaping from primary lesion of cancer to brain are strictly regulated by blood-brain barrier and therefore cerebrospinal fluid (CSF) circRNAs have potential advantage in exploring biomarkers and mechanism of brain metastasis in lung cancer. METHODS: We collected paired cerebrospinal fluid, plasma and tumor tissues from 21 lung adenocarcinoma (ADC) patients with brain metastases (BM) and performed RNA sequencing. RESULTS: Compared to tumor tissue and plasma, circRNAs in CSF were characterized by lower number of spieces but higher abundance. Notably, CSF-circRNAs displayed high heterogeneity among different BM lung ADC patients. A total of 60 CSF-circRNAs was identified and associated with shorten overall survival. The circRNA-miRNA-mRNA network analysis revealed that the 60 CSF-circRNAs involved in cancer-associated pathways, and five of them showed strong association with WNT signaling pathway. Validation by RT-PCR of CSF and in vitro experiments of the five candidate circRNAs support their potential roles in cell proliferation and invasion. CONCLUSIONS: In summary, our results depicted the heterogenous CSF-circRNAs profiles among BM lung ADC and implied that CSF-circRNAs may be promising prognosis-related biomarkers.