Extracellular vesicle-derived circHIPK3: Novel diagnostic biomarker for lung cancer

Lung cancer (LC) is a common malignancy worldwide. A great number of circular RNAs (circRNAs) have been identified that serve crucial roles in cancer development. Extracellular vesicles (EVs) and their contents have been shown to be biomarkers for the diagnosis and prognosis of LC. Thus, we intended to clarify the functional role of EVs-derived circRNA homology domain interacting protein kinase 3 (EVs-circHIPK3) and its underlying mechanism of action.

Bioinformatics analysis was performed to validate the potential of partially circulating HIPK3 in LC diagnosis. EVs were isolated by polyethylene glycol (PEG) precipitation from plasma of 52 LC patients and 30 healthy controls. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was employed to evaluate the expressions of candidate circRNAs (circHIPK3) and microRNA-637 (miR-637, a target of circHIPK3).

CircHIPK3 is significantly up-regulated in LC, while miR-637 expression is significantly reduced (p ​< ​0.05). Receiver operating characteristic (ROC) curve analysis, based on the expression of EVs-circHIPK3, allowed us to distinguish LC from healthy controls (area under the curve, AUC 0.897).

Taken together, our study shows that EV-derived circHIPK3 can serve as a promising biomarker for LC patient diagnosis. However, the downstream mRNA of the circHIPK3/miR-637 axis requires further exploration to enrich our understanding of circHIPK3's mechanism in LC.