Epigenetic signature discriminates lymphatic metastasis in BRAF wild-type thyroid carcinoma: methylation role of GRIK2

Author:

Peng Jin1ORCID,Zhang Qingfeng1,Lin Fei2,Ke Chao1,Deng Wuguo1,Yang Ankui1,Su Xuan1ORCID

Affiliation:

1. State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China

2. Department of Oncology, Guangdong Provincial Hospital of Integrated Traditional Chinese & Western Medicine, Affiliated Nanhai Hospital of Traditional Chinese Medicine of Jinan University, Foshan, Guangdong Province, 528200, China

Abstract

Aim: Conservative treatment approaches for thyroid carcinoma (TC) patients with wild-type B-type Raf kinase ( BRAF) pose risks of long-term recurrence. The association of DNA methylation with TC metastasis is unclear. Patients & methods: Here we analyzed data from 179 BRAF wild-type TC patients in the The Cancer Genome Atlas database, identifying significant metastasis-associated CpGs. A logistic regression model was developed and validated for discriminating lymphatic metastasis in BRAF wild-type TC. Results: The model showed high accuracy (AUC: 0.924 training set; 0.812 and 0.773 external cohorts). TAGLN, MRPL4, CLDN10 and GRIK2 emerged as diagnostic markers. GRIK2, downregulated due to promoter hypermethylation, acted as a TC suppressor. Conclusion: Our 5-CpG epigenetic signature effectively discriminates lymphatic metastasis in BRAF wild-type TC, highlighting GRIK2‘s tumor-suppressive role influenced by promoter hypermethylation.

Funder

National Natural Science Foundation of China

Guangdong Basic and Applied Basic Research Foundation

Natural Science Foundation of Guangdong Province

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

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