CT and positron emission tomography can
(CT) and positron emission tomography can detect tumours with a diameter of about 2–6 mm. Low-dose spiral CT has high sensitivity and avoids other traumatic examinations. However, owing to its high sen-sitivity, the false positive rate is high, leading to over-diagnosis, false alarms, and unnecessary examinations, biopsies, and operations (Stanley, 2001; Swensen et al., 2003). Therefore, the identification of true positives and false positives after screening by low-dose CT is an urgent issue.
Lung tissue biopsy can provide high diagnostic accuracy. However, this approach is inconvenient and invasive and may lead to additional
∗ Corresponding author. State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China.
∗∗ Corresponding author. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200443, China. E-mail addresses: [email protected] (C. Chen), [email protected] (H. Mao). 1 Yanan Bai and Youlan Qu contribute to this work equally.
complications (Bensard et al., 1993; Yung, 2003). There is thus a cri-tical need for non-invasive and highly sensitive diagnostic methods to improve early diagnosis and outcomes. Bodily fluids, such as blood, are considered ideal samples for disease diagnosis (Goessl et al., 2001; Johnson and Lo, 2002). Prior research has shown that extracellular vesicles (EVs), including exosomes and microvesicles, can be readily harvested from the blood for further analysis and thus represent an attractive source of tumour-derived materials (Yanez-Mo et al., 2015).
EVs are specialized membranous, nanosized endocytic vesicles that are secreted by most Z-Guggulsterone (Colombo et al., 2014). In particular, EVs secreted from tumour cells are closely related to tumour development, immune escape, and the tumour microenvironment (Kalluri, 2016). They are abundant, stable, and contain unique proteins and nucleic acids (e.g. DNAs, mRNAs, miRNAs, and lncRNAs) reflective of their cells of origin (Mateescu et al., 2017; Thakur et al., 2014). Emerging evidence indicates that long non-coding ribonucleic acids (lncRNAs) from the peripheral blood are potential cancer biomarkers. LncRNAs are defined as transcripts with a minimum length of 200 nucleotides and limited protein-coding potential; deregulated expression can not only diﬀerentiate normal populations and patients with lung cancer but is also associated with the occurrence and development of lung cancer (Mercer et al., 2009; Ponting et al., 2009). In our previous study, we screened diﬀerentially expressed lncRNAs in early lung cancer tissues and demonstrated that they may be clinically useful biomarkers for early diagnosis (Cheng et al., 2017; Wang et al., 2015). However, owing to the diﬃculty in obtaining tissue samples from patients suspected to have lung cancer, the development of a sensitive, accurate, and cost-eﬀective method using circulating, EV-lncRNAs as biomarkers is needed for diagnosis.
Existing lncRNA detection methods include quantitative real-time polymerase chain reaction (qPCR) (Schmittgen et al., 2008; Shi and Chiang, 2005), microarray (Akama et al., 2009; Liu et al., 2008), next-generation sequencing (Chen et al., 2009), and surface-enhanced Raman spectroscopy (SERS) (Driskell et al., 2008). SERS-based methods are limited by a lack of spectral reproducibility of the SERS substrate for early detection. Next-generation sequencing-based molecule counting relies on complex library preparation schemes, and high sequencing depths are required to achieve high sensitivity. Using microarray and qPCR methods, it is diﬃcult to detect targets with low copy numbers. It has been reported that the content of lncRNAs in EVs is very low; far lower than their mRNA level (Li et al., 2019). Therefore, there is a need for a more sensitive, accurate, and convenient quantitative method to study low-abundance EV-lncRNA.