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Profiling genome-wide circulating ncRNAs for the early detection of lung cancer

Award Number: R01CA223490
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2018
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Profiling genome-wide circulating ncRNAs for the early detection of lung cancer - PROJECT SUMMARY 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cancer Detection and Diagnosis Research	000	5	9/18/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $715,805 )
2022	2022	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cancer Detection and Diagnosis Research	001	5	8/24/2022	NON-COMPETING CONTINUATION	$481,680
2022	2021	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cancer Detection and Diagnosis Research	000	4	2/17/2022	NON-COMPETING CONTINUATION	$234,125
														Subtotal = $715,805

Issue Date FY: 2021 ( Subtotal = $534,396 )
2021	2021	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cancer Detection and Diagnosis Research	000	4	8/27/2021	NON-COMPETING CONTINUATION	$534,396
														Subtotal = $534,396

Issue Date FY: 2020 ( Subtotal = $744,062 )
2020	2020	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cancer Detection and Diagnosis Research	001	3	9/1/2020	SUPPLEMENT FOR EXPANSION	$233,375
2020	2020	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cancer Detection and Diagnosis Research	000	3	8/19/2020	NON-COMPETING CONTINUATION	$510,687
														Subtotal = $744,062

Issue Date FY: 2019 ( Subtotal = $535,765 )
2019	2019	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cancer Detection and Diagnosis Research	000	2	8/22/2019	NON-COMPETING CONTINUATION	$535,765
														Subtotal = $535,765

Issue Date FY: 2018 ( Subtotal = $565,835 )
2018	2018	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cancer Detection and Diagnosis Research	000	1	8/29/2018	NEW	$565,835
														Subtotal = $565,835

Grand Total All Awards = $3,095,863

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Profiling genome-wide circulating ncRNAs for the early detection of lung cancer

Award Number: R01CA223490

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2018

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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