Abstract 1445P
Background
Cardia gastric adenocarcinoma (CGA) and esophageal squamous cell carcinoma (ESCC) remain major health burdens in China. Most of cases are diagnosed at advanced stages and carry a dismal prognosis. However, biomarkers for early detection of CGA and ESCC are still lacking. Here, we integrated methylome and transcriptome data and identified tumor-specific and tumor-shared DNA methylation markers for early detection of CGA and ESCC.
Methods
Infinium MethylationEPIC array was performed on 36 paired CGA and non-tumor adjacent tissues (NAT) in the discovery stage and differentially methylated CpG sites (DMCs) were identified between CGA/ESCC and NAT by combined analyses of in-house data and public database. Targeted pyrosequencing and quantitative real-time RT-PCR were performed on paired tumor and NAT from 50 CGA and 50 ESCC patients in the validation stage. An independent cohort of 438 CGA, ESCC, high- and low-grade dysplasia (HGD/LGD), and normal control biopsies was tested for selected DMCs using pyrosequencing.
Results
We identified and validated three CGA-specific, two ESCC-specific, and one tumor-shared DMCs, which were significantly hypermethylated with lower expression of their located genes in tumor compared with NAT samples. Using these DMCs, we developed a CGA-specific 4-marker panel (cg27284428, cg11798358, cg07880787, and cg00585116) that discriminated cardia HGD/CGA patients from cardia LGD/normal controls with the area under ROC curve (AUC) of 0.917, and an ESCC-specific 3-marker panel (cg14633892, cg04415798, and cg00585116) distinguishing esophageal HGD/ESCC with AUC of 0.865. Integrating cg00585116, age, and alcohol drinking, the tumor-shared model showed good discrimination for two cancer/HGD in the training set with AUC of 0.740, which was confirmed in the test set with AUC of 0.841.
Conclusions
Collectively, novel DNA methylation markers could differentiate CGA/ESCC and HGD from LGD and normal controls with promising accuracy. Our findings pave the way for targeted DNA methylation assays in future minimally invasive cancer screening methods.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1937P - Clinical characteristics and prognosis of pediatric patients with papillary thyroid carcinoma
Presenter: Junko Akaishi
Session: Poster session 18
1938P - Nomogram for predicting lung metastases in patients with papillary thyroid cancer under 55 years old
Presenter: Huiyun Yang
Session: Poster session 18
1939P - BrafV600E-induced cancer inflammation in a mouse model of thyroid tumorigenesis
Presenter: Sima Kumari
Session: Poster session 18
1940TiP - Sacituzumab govitecan in patients with advanced or metastatic radioactive-iodine refractory thyroid carcinoma and anaplastic thyroid carcinoma: The phase II SETHY, GETNE-T2318 trial design
Presenter: Alejandro Garcia Alvarez
Session: Poster session 18
1941TiP - Neoadjuvant pembrolizumab in high-risk thyroid cancer (NePenTHe)
Presenter: Claudia Leli
Session: Poster session 18
1924P - Efficacy and safety of lenvatinib in patients with chemotherapy-naive advanced or recurrent thymic carcinoma: A multicenter retrospective study
Presenter: Daisuke Hazama
Session: Poster session 18
1923P - Real-world management and outcome of thymic carcinomas in a tertiary German center
Presenter: Antonia Margineanu
Session: Poster session 18
1922P - Targeted resequencing designed specifically for thymic epithelial tumours confirmed the high prevalence of GTF2I mutations
Presenter: Iacopo Petrini
Session: Poster session 18
1921P - Molecular analysis of mesothelioma reveals mutations as prognostic biomarkers for patients treated with the combination of ipilimumab and nivolumab
Presenter: Angelica Rigutto
Session: Poster session 18
1920P - Multiomics analysis of malignant pleural mesothelioma and the effect of immune checkpoint inhibitors
Presenter: Akiko Tateishi
Session: Poster session 18