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
4653 - Impact of Pembrolizumab (pembro) Versus Paclitaxel on Health-Related Quality of Life (HRQoL) in Patients With Advanced Gastric or Gastroesophageal Junction (GEJ) Cancer That Has Progressed After First-Line Chemotherapy (KEYNOTE-061)
Presenter: Eric Van Cutsem
Session: Poster Display session 2
Resources:
Abstract
5063 - Does Nutritional Status Affect Treatment Tolarability, Response and Survival in Metastatic Gastric Cancer Patients? Results of Prospective Multicenter Study
Presenter: Senem Karabulut
Session: Poster Display session 2
Resources:
Abstract
2717 - Ramucirumab use in patients with Advanced Gastric Cancer (AGC) or gastro-oesophageal junction (GEJ) adenocarcinoma in Spain: RAMIS observational study
Presenter: Federico Longo Munoz
Session: Poster Display session 2
Resources:
Abstract
3187 - Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor: Exploratory analysis in the patients who were enrolled in JCOG0705/KGCA01 phase III trial (REGATTA) and could continue chemotherapy
Presenter: Takaki Yoshikawa
Session: Poster Display session 2
Resources:
Abstract
4765 - A prospective observational study on the optimal maintenance strategy in HER2-positive advanced gastric cancer treated with trastuzumab based therapy
Presenter: Qian Li
Session: Poster Display session 2
Resources:
Abstract
3500 - Randomised phase 2 trial of first-line docetaxel, carboplatin, capecitabine (CTX) and epirubicin, oxaliplatin, capecitabine (EOX) in advanced esophagogastric adenocarcinoma (SEED)
Presenter: Peter Petersen
Session: Poster Display session 2
Resources:
Abstract
5197 - Ramucirumab in the treatment of refractory metastatic gastric cancer: results from the RamSelGa trial.
Presenter: Alexey Tryakin
Session: Poster Display session 2
Resources:
Abstract
2011 - Regorafenib in combination with Paclitaxel for beyond first-line treatment of advanced esophagogastric cancer (REPEAT): a phase Ib trial with expansion cohort
Presenter: Mohammed Khurshed
Session: Poster Display session 2
Resources:
Abstract
2117 - The relationship between the survival and fixed dosing of S-1 in advanced gastric cancer patients by pooled analysis using individual data from four Japanese randomized phase III trials
Presenter: Wataru Ichikawa
Session: Poster Display session 2
Resources:
Abstract
2669 - A Phase 1b Study of Oraxol in Combination with Ramucirumab in Patients with Gastric or Esophageal Cancers who failed previous chemotherapy
Presenter: Ming Huang Chen
Session: Poster Display session 2
Resources:
Abstract