Circulating hsa_circ_0072309, acting via the miR‐100/ACKR3 pathway, maybe a potential biomarker for the diagnosis, prognosis, and treatment of brain metastasis from non‐small‐cell lung cancer

Abstract

Abstract Background One of the main causes of lung cancer‐related death is brain metastasis (BM). Finding early indicators of BM derived from lung cancer is crucial. Therefore, this study was designed to determine if serum hsa_circ_0072309 may be employed as a potential biomarker for BM induced by non‐small‐cell lung cancer (NSCLC) and to understand its possible underlying mechanism. Methods Primary lung cancer and healthy neighboring tissues were obtained from all patients, while BM tissues were taken from BM+ patients. Serum specimens were collected from all patients and healthy volunteers. Hsa_circ_001653, miR‐100, and ACKR3 RNA expressions were analyzed by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR), and atypical chemokine receptor 3 (ACKR3) protein expression by western blotting (WB), immunohistochemistry (IHC), and enzyme‐linked immunosorbent assay (ELISA). In order to examine the effect of serum hsa_circ_0072309 and its relevant mechanism on BM development, an NSCLC‐associated BM model in mice was established. Results According to the results, miR‐100 expression was down‐regulated in primary lung cancer tissues compared to healthy lung tissues in all NSCLC patients, and circ_0072309 and ACKR3 expression were up‐regulated. In BM tissues compared with primary lung tumors of BM+ patients, in serum samples from all patients compared to healthy volunteers, and in lung tumors of BM+ patients compared to those from BM− patients. Patients' serum exhibits the same level of hsa_circ_0072309/miR‐100/ACKR3 expression as in BM samples. Advanced tumor‐node‐metastasis (TNM) stage, higher BM, shorter post‐operative overall survival (OS), and progression‐free survival (PFS) are all substantially associated with increased serum circ_0072309 levels in BM+ patients. In animal models, serum owning hsa_circ_0072309 from BM+ patients facilitates BM formation by regulating the miR‐100/ACKR3 pathway. Conclusions The current preliminary research reveals serum hsa_circ_0072309 as a possible biomarker and target for early diagnosis, prognosis, and therapy of NSCLC‐derived BM and suggests a substantial role for the hsa_circ_0072309/miR‐100/ACKR3 axis in the formation of BM from NSCLC.

Keywords

• diagnostic biomarker
• miR‐100/ACKR3 signal
• NSCLC‐associated brain metastasis
• serum hsa_circ_0072309
• therapeutic target