Abstract 5051
Background
A rapid increase in incidence of thyroid cancer has been reported in recent years. However, ambiguities between benign and malignant nodules in cytological features have led to unnecessary thyroidectomy or over-treatment. We aimed to identify DNA methylation markers to accurately classify thyroid nodules, which may be developed into non-invasive screening diagnostics for thyroid cancer to reduce unnecessary thyroid removals.
Methods
Genome-wide DNA methylation profiles of papillary thyroid cancer nodules (tissue, N = 37; plasma, N = 55), benign nodules (tissue, N = 37; plasma, N = 55) and healthy samples (buffy coat, N = 20; plasma, N = 123) were generated by a modified RRBS method. An independent RRBS dataset including 89 malignant and 72 benign nodules was derived from Yim et al. 2019. We adopted Singlera’s MONOD+ assay to interrogate the methylation state of over 4,000,000 CpG sites across more than 200,000 methylation haplotype blocks (MHBs). We identified discriminatory DNA methylation MHBs by Wilcox rank sum test. Using our dataset as a training set, we built several diagnostic models to classify thyroid nodules using machine learning methods. We validated the model by classifying public methylation datasets of thyroid tissues.
Results
We generated an initial list of top 1000 DNA methylation markers and built a classification model by the random forest method. We classified DNA methylation profiles of thyroid nodules published by Yim et al. 2019. Results show that this model achieved a sensitivity of 82%, a specificity of 94.4% and AUC of 0.94 (95% CI, 0.91-0.98). We randomly selected the 2/3 plasma samples as training data to build a prediction model. The model yielded an accuracy of 72% in the validation cohort. We also identified 2392 deferentially methylated regions by comparing benign tissues with malignant tissues. DMR associated genes are highly enriched in many cancer related pathways and MSigDB immunologic signatures, indicating the development of thyroid cancer is closely associated with immune dysfunction.
Conclusions
Our study demonstrates that DNA methylation markers can robustly differentiate thyroid nodules. They are thus promising candidates to develop non-invasive diagnostics for thyroid cancer screening.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The First Affiliated Hospital of Sun Yat-sen University.
Funding
National Natural Science Foundation of China (81772850).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
870 - Selective Wnt/β-catenin small-molecule inhibitor CWP232228 impairs tumor growth of colon cancer
Presenter: Jin Young Kim
Session: Poster Display session 2
Resources:
Abstract
3425 - Feasibility and impact of prospective DPYD screening in the Irish population
Presenter: Mohammed Zameer
Session: Poster Display session 2
Resources:
Abstract
1972 - Diet-derived metabolites and the risk of colorectal cancer: a nested case-control study in a population-based cohort, the Singapore Chinese Health Study
Presenter: Dawn Chong
Session: Poster Display session 2
Resources:
Abstract
4103 - Loss of subcutaneous adipose tissue during chemotherapy predicts reduced survival in patients with incurable colorectal cancer undergoing palliative therapy
Presenter: Erin Stella Sullivan
Session: Poster Display session 2
Resources:
Abstract
4309 - Obese and overweight is associated with better prognosis in metastatic colorectal cancer patients treated with bevacizumab.
Presenter: Bozena Cybulska-Stopa
Session: Poster Display session 2
Resources:
Abstract
3554 - Patient characteristics associated with poor performance status, ECOG 2-3, and effect on survival in 1086 Finnish metastatic colorectal cancers (mCRC) nationwide (prospective RAXO study)
Presenter: Pia Österlund
Session: Poster Display session 2
Resources:
Abstract
4572 - Discovery and Diagnosis of Metastatic Colorectal Cancer (mCRC) in the Real World: Final Results from a European Survey
Presenter: Iga Rawicka
Session: Poster Display session 2
Resources:
Abstract
4783 - Adherence to recommended intake of calcium and colorectal cancer risk in the HEXA study
Presenter: Jeeyoo Lee
Session: Poster Display session 2
Resources:
Abstract
5106 - Body size, sex and sidedness of incident colorectal cancer in a prospective Swedish cohort study
Presenter: Christina Siesing
Session: Poster Display session 2
Resources:
Abstract
3364 - Middle East & North Africa Registry to characterize RAS mutation status and tumor specifications in recently diagnosed patients with metastatic colorectal cancer (MORE-RAS Study)
Presenter: Mohamed Oukkal
Session: Poster Display session 2
Resources:
Abstract