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
3911 - Defining a SUV decrease cut-off in PET/CT response monitoring after one cycle of preoperative breast cancer chemotherapy
Presenter: Marcin Kubeczko
Session: Poster Display session 2
Resources:
Abstract
1849 - Effect of thioredoxin 1 quantity detection to complement the mammography in breast cancer diagnosis
Presenter: Younju Lee
Session: Poster Display session 2
Resources:
Abstract
2221 - Identification of ultralow risk breast cancer patients (probable overdiagnosis)
Presenter: Salvador Gamez Casado
Session: Poster Display session 2
Resources:
Abstract
5291 - Prevalence of Vitamin D3 deficiency among women with early breast cancer receiving chemotherapy in an oncology dayward.
Presenter: Warner Finstad
Session: Poster Display session 2
Resources:
Abstract
4247 - Changes in ER pathway activity score during neoadjuvant letrozole to assess therapy response and predict disease free survival (DFS) in ER positive breast cancer patients
Presenter: Arran Turnbull
Session: Poster Display session 2
Resources:
Abstract
568 - Second primary malignancies in patients with breast cancer.
Presenter: Carlos Erasun Lecuona
Session: Poster Display session 2
Resources:
Abstract
1428 - Phase II randomized trial of neoadjuvant trastuzumab and pertuzumab (TP) with either palbociclib + letrozole (Pal+L) or paclitaxel (Pac) for elderly patients with estrogen receptor & HER2 positive (ER+/HER2+) Breast Cancer (BC) (International Breast Cancer Study Group IBCSG 55-17, TOUCH)
Presenter: Laura Biganzoli
Session: Poster Display session 2
Resources:
Abstract
1479 - Neoadjuvant HER2-targeted therapy with or without immunotherapy with pembrolizumab (neoHIP): an open label randomized phase 2 trial
Presenter: Heather McArthur
Session: Poster Display session 2
Resources:
Abstract
1481 - A randomized phase 2 study of peri-operative ipilimumab, nivolumab and cryoablation versus standard care in women with residual, early stage/resectable, triple negative breast cancer after standard-of-care neoadjuvant chemotherapy
Presenter: Heather McArthur
Session: Poster Display session 2
Resources:
Abstract
4334 - ALEXANDRA/IMpassion030: A phase 3 study of standard adjuvant chemotherapy with or without atezolizumab in early stage triple negative breast cancer.
Presenter: Michail Ignatiadis
Session: Poster Display session 2
Resources:
Abstract