Evaluation of EpCAM-specific exosomal lncRNAs as potential diagnostic biomarkers for lung cancer using droplet digital PCR

被引:25
|
作者
Shen, Xintong [1 ,2 ,3 ]
Yang, Yifeng [1 ,2 ,3 ]
Chen, Yinfeng [1 ,2 ,3 ]
Zhou, Chengwei [1 ]
Zhao, Xiaodong [1 ]
Li, Nan [4 ]
Lou, Chengtao [1 ,2 ,3 ]
Huang, Ying [1 ,2 ,3 ]
Tian, Dongmei [1 ,2 ,3 ]
Shen, Yan [1 ,2 ,3 ]
Meng, Xiaodan [1 ,2 ,3 ]
机构
[1] Ningbo Univ, Affiliated Hosp, Med Sch, Dept Thorac Surg, 247 Renmin Rd, Ningbo 315020, Zhejiang, Peoples R China
[2] Ningbo Univ, Med Sch, Dept Biochem & Mol Biol, 818 Fenghua Rd, Ningbo 315211, Zhejiang, Peoples R China
[3] Ningbo Univ, Med Sch, Zhejiang Prov Key Lab Pathophysiol, Ningbo 315211, Zhejiang, Peoples R China
[4] Zhengzhou Univ, Affiliated Hosp 1, Clin Lab, Zhengzhou 450052, Henan, Peoples R China
来源
JOURNAL OF MOLECULAR MEDICINE-JMM | 2022年 / 100卷 / 01期
基金
中国国家自然科学基金;
关键词
EpCAM-specific exosomes; Lung cancer; Diagnosis; Lung adenocarcinoma; Squamous cell lung cancer; Digital polymerase chain reaction; STATISTICS; BLOOD;
D O I
10.1007/s00109-021-02145-4
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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. EpCAM-specific exosomal PHEX-AS1 is associated with lung cancer progression.
引用
收藏
页码:87 / 100
页数:14
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