Abstract

Abstract Accumulating evidence demonstrated that long non-coding RNAs (lncRNAs) derived from exosomes had the potential to be diagnostic markers for lung cancer. However, the diagnostic value of lncRNAs from epithelial cell adhesion molecule (EpCAM)–positive exosomes remains unclear. In the study, serum EpCAM-positive exosomes were isolated with magnetic beads, and their role in lung cancer was investigated in vitro and in vivo. The copy numbers of lncRNAs RP11-77G23.5 and PHEX-AS1 in EpCAM-specific exosomes were quantified by droplet digital PCR (ddPCR). The diagnostic value of RP11-77G23.5 and PHEX-AS1 was tested in the training cohort and verified in the validation cohort. We found that EpCAM-specific exosomes could promote lung cancer development in vitro and in vivo. RP11-77G23.5 and PHEX-AS1 were significantly elevated in EpCAM-specific exosomes from lung cancer patients and could distinguish malignant from benign lung tumors. The amounts of RP11-77G23.5 were statistically higher in the subtype of lung adenocarcinoma (LUAC) than that of lung squamous cell carcinoma (LUSC), showing its capability to subtype LUAC and LUSC, while PHEX-AS1 exhibited distinct expression signatures between lower and higher tumor stages, and without and with distant metastasis, indicating its association with lung cancer progression. In conclusion, the EpCAM-specific exosomal lncRNAs RP11-77G23.5 and PHEX-AS1 may be promising diagnostic biomarkers for lung cancer. Key messages Serum EpCAM-positive exosomes promote lung cancer development in vitro and in vivo. Two EpCAM-specific exosomal lncRNAs can be simultaneously detected by RT-ddPCR. EpCAM-specific exosomal RP11-77G23.5 has the potential to subtype LUAC and LUSC.