Clinical trial NCT04814407: Developing Novel Circulating Epigenetic Biomarkers for Early Detection of Lung Cancer
Official title: Developing Novel Circulating Epigenetic Biomarkers for Early Detection of Lung Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Lung Cancer
Keywords: Lung cancer
Cell-free DNA
DNA methylation
T cell methylome
cell-free tumor DNA (ctDNA)
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2021-03-24
Enrollment: 900
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1. Study subjects: Patients with suspected or confirmed diagnosis of lung cancer.
2. Indeterminate subjects: Subjects who had indeterminate sub-centimeter pulmonary nodules or ground glass opacities discovered by computed tomography.
3. Control subjects: Non-cancer subjects including healthy volunteers, chronic inflammatory airway diseases such as chronic obstructive airway disease, asthma, and bronchiectasis, etc.

Brief summary: The investigators aim to identify novel circulating methylated biomarkers for early lung cancer detection as well as to develop new technologies that are clinically applicable with high sensitivity and specificity.

Detailed description: Lung cancer is the leading cause of cancer death, accounting for 2.09 million cases in 2018 worldwide. There is a huge demand globally for sensitive and reliable assays to intercept lung cancer at early stages when it can be cured. Past studies have shown that circulating cell-free tumor DNA (ctDNA) shed from tumor cells contains the same mutations and methylation patterns as the original tumor cells. Emerging evidence has indicated the presence of systemic immune dysregulation in cancer patients, and that tumor-reactive T cells carry a distinct molecular profile compared to other bystander cells. Thus, molecular abnormality of ctDNA and tumor-reactive T cells may be one of the early signs that hint the presence of malignancy, and it may serve as a promising target for development of blood-based assays in early lung cancer for its convenience and non-invasiveness as opposed to invasive tumor biopsy, or imaging-based methods that are limited by unsatisfactory sensitivity/specificity.

The investigators aim to identify novel markers for early lung cancer detection as well as to develop new technologies that are clinically applicable with high sensitivity and specificity. The objectives of this proposal are multifaceted: (1) The investigators will generate genome-wide methylation atlas of circulating cell free DNA and of circulating T cells in lung cancer patients vs. non-cancer subjects. (2) The investigators will develop an enriched method to enhance the performance of multiplex droplet digital PCR (ddPCR) technology with increased sensitivity and decreased input DNA requirement. (Enriched methylation-specific droplet digital PCR, EMS-ddPCR) (3) The investigators will develop a single-cell, locus-specific DNA methylation detection system that is bisulfite-free and non-PCR-based. The system can be coupled with flow cytometry or mass cytometry to enable cell-type specific methylation detection. (single-cell, locus-specific methylation detection, scLSM-FACS) (4) The investigators will identify a novel methylation signature consisting of tumor-derived and immune-derived biomarkers for early detection of lung cancer.

Eligibility criteria: Inclusion Criteria:

* Subjects suspected or confirmed diagnosis of lung cancer.
* Subjects who had indeterminate sub-centimeter pulmonary nodules or ground glass opacities discovered by computed tomography.
* Non-cancer subjects: including healthy volunteers and chronic inflammatory airway diseases such as chronic obstructive airway disease, asthma, and bronchiectasis, etc.
* Subjects age over 20.

Exclusion Criteria:

* Pregnancy.
* Subjects with HIV infection.
* Unable to or unwilling to give informed consent.

Primary outcomes:
measure: Identification of circulating tumor and immune methylated signature
timeFrame: 1 year
measure: Technology development
timeFrame: 1 year
measure: Technology validation
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Graduate institute of Toxicology, NTUCM; Department of Internal Medicine, NTUH
name: Hsing-Chen Tsai, M.D., Ph.D
role: STUDY_CHAIR
References: