The 5-year survival for patients with lung cancer remains dismal at approximately 15%. It has been
estimated that early diagnosis of lung cancer can provide a 60-80% survival benefit. The National Lung
Screening Trial (NLST) demonstrated a 20% relative reduction in lung cancer mortality with the use of annual
low-dose computed tomography (LDCT) screening compared to annual chest x-ray. The difference in lung
cancers identified was due to the identification of more early-stage lung cancers, as there was no difference in
the number of stage IIB-IV cancers between groups. The authors concluded that LDCT screening reduced lung
cancer mortality in appropriately selected high-risk patients. Unfortunately, nearly 40% of patients in the NLST
had a positive screen at one point, with 96.4% of these being false positives. Accordingly, the International
Association for the Study of Lung Cancer (IASLC) and the Strategic CT Screening Advisory Committee
(SSAC) published a position statement calling for the increased use of blood-based biomarkers to augment the
diagnostic accuracy of LDCT screening, so it is urgently necessary to develop new non-invasive methods,
such as identifying blood molecular biomarkers, for early detection of lung cancer.
Our immediate objective for this proposal is to identify circulating non-coding RNA (ncRNA) markers for the
early detection of lung cancer using prospectively collected human blood samples. Very few studies have
compared the expression profiles of circulating miRNA between benign lesions and lung cancer. Therefore, it
is important to validate existing miRNA studies and identify potential novel circulating miRNA markers for early
detection of lung cancer. In addition, recent studies have shown that other types of small ncRNAs such as
small nucleolar RNAs (snoRNAs) and transfer RNAs (tRNAs) play important roles in cancer development and
progression. However, there are no reports which use other types of circulating small ncRNAs as markers for
lung cancer early detection.
We hypothesize that circulating ncRNA could be used as biomarkers for early detection of lung cancer.
Based on next generation small RNA sequencing, we have identified circulating plasma ncRNAs that are
significantly differentiated in expression between non-malignant and lung cancer biospecimens. Moreover,
although a series of publications have reported the potential circulating miRNA markers for early detection of
lung cancer, they are quite inconsistent. In order to increase our sequencing power, evaluate our previous
finding and other published biomarkers for early detection of lung cancer. Using prospectively collected plasma
samples, in the proposed study, we would like to reach the following aims: 1. Measure the types and levels of
ncRNA expression in human plasma from non-malignant and lung cancer biospecimens. 2. Evaluate ncRNA
markers that vary reproducibly between non-malignant samples and lung cancer samples based on the real-
time PCR platform. 3. Validate and test the predictive value of the ncRNA markers using independent samples.