# Developing a CLIA compliant LDT for detecting plasma piR-Ls/pfeRNAs to distinguish benign and malignant lung nodules

> **NIH NIH UH3** · JOHNS HOPKINS UNIVERSITY · 2020 · $331,594

## Abstract

Project Summary:
Lung cancer is the leading cause of cancer-related death in the U.S., in large part, because the diagnosis tends
to be made after the cancer has progressed to its most advanced stages. However, current diagnostic techniques
for detecting early-stage non-small cell lung cancer (NSCLC) are either invasive or have poor accuracy. We
recently reported that piRNA-like sncRNAs (piR-Ls) and protein function effector sncRNAs (pfeRNAs) play
critical roles in the tumorigenesis and differentiation of lung cancer. We have developed a novel technology for
accurately and robustly measuring piR-Ls and pfeRNAs in plasma. We also have identified 2 piR-Ls and 6
pfeRNAs as promising non-invasive biomarkers using next generation sncRNAs deep sequencing of 119
biospecimens, including (i) plasma from healthy controls (ii) patient plasma with the matched, corresponding
histologically proven NSCLC tissue as well as histologically normal adjacent lung tissue from patients with Stage
I/II NSCLC (iii) plasma from patients with both biopsy proven benign and malignant lung nodules. Furthermore,
we validated these biomarkers in 352 clinical plasma specimens, including 77 healthy controls, 44 patients with
benign disease as well as 231 patients with malignant lung nodules. Moreover, we formulated prediction rules
for our assay in detecting early-stage NSCLC. Using only plasma, we were able to: (1) differentiate patients with
and without lung nodules, with a sensitivity and specificity of 98.5% and 98.7%, respectively (an important clinical
assay needed in remote, impoverished areas of the world with a high prevalence of smokers but no access to
CT scanning); (2) differentiate patients who had malignant versus benign lung nodules, with a sensitivity and
specificity of 96.5% and 72.7%, respectively (important for economically advanced countries enrolling smokers
to CT lung cancer screening programs). These data strongly suggest that our panel of 2 piR-Ls and 6 pfeRNAs
are non-invasive putative biomarkers for detecting early-stage lung cancers. Our multi-disciplinary collaborative
team consists of a physician-scientist, basic researchers, a physician-scientist in the CLIA-certified laboratory,
statisticians, and a commercial developer. This team will develop a CLIA compliant LDT for validating our nucleic-
acid-based existing assay which now has been tested as valid in over 460 clinical specimens. The technologies
that we will utilize for our testing are currently FDA-cleared for use in clinical laboratories, and the equipment as
well as all reagents for our assays already are used in in-vitro-diagnostic testing. Our collaborative team aims to
develop a molecular diagnostic assay that can be integrated into future clinical trials for the early detection of
NSCLC, and ultimately, improve the dismal survival rates of that disease.

## Key facts

- **NIH application ID:** 9908056
- **Project number:** 5UH3CA239137-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** MALCOLM V BROCK
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $331,594
- **Award type:** 5
- **Project period:** 2019-04-05 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908056

## Citation

> US National Institutes of Health, RePORTER application 9908056, Developing a CLIA compliant LDT for detecting plasma piR-Ls/pfeRNAs to distinguish benign and malignant lung nodules (5UH3CA239137-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9908056. Licensed CC0.

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