, Volume 66, Issue 3, pp 573–584 | Cite as

Identification of gene co-expression modules and hub genes associated with lymph node metastasis of papillary thyroid cancer

  • Tianyu Zhai
  • Dilidaer Muhanhali
  • Xi Jia
  • Zhiyong Wu
  • Zhenqin Cai
  • Yan LingEmail author
Original Article


Papillary thyroid cancer (PTC) is the most prevalent histological type among thyroid cancers, and some patients are at a high risk for recurrent disease or even death. Identification for the potential biomarkers of PTC may contribute to early discovery of recurrence and treatment. In The Cancer Genome Atlas (TCGA) database, we obtained the information of RNA sequence data and clinical characteristics of PTC. Weighted gene co-expression network analysis (WGCNA) was performed to construct gene co-expression networks and investigate the relationship between modules and clinical traits. Finally, we constructed 16 co-expression modules in 10,428 genes, and three key modules (darkturquoise, lightyellow, and red) associated with tumor N grade were identified. The results of functional annotation indicated that the darkturquoise module was primarily enriched in the regulation of the extracellular matrix (ECM), collagen metabolism, and cell adhesion, the lightyellow module was primarily enriched in the mitochondrial function regulation and energy synthesis, and the red module was primarily enriched in the process of cell junction, apoptosis, and inflammatory response, suggesting their significant role in the progression of PTC. In addition, the hub genes in the three modules were identified and screened for differentially expressed genes (DEGs). Relapse-free survival analyses found that 11 genes (KCNQ3, MET, FN1, ITGA3, RUNX1, ITGA2, PERP, GCSH, FAAH, NGFRAP1, and HSPA5) may play a pivotal role in PTC relapse. In general, our research revealed the key co-expression modules and identified several prognostic biomarkers, which provides some new insights into the lymph node metastasis of PTC.


Papillary thyroid cancer Weighted gene co-expression network analysis Hub genes Lymph node metastasis 



We thank all the authors for their contributions.


This study was funded by the National Natural Science Foundation of China (grant number 81402207).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Supplementary Figure1.
12020_2019_2021_MOESM2_ESM.tif (872 kb)
Supplementary Figure2.
12020_2019_2021_MOESM3_ESM.docx (20 kb)
Supplementary Tables.


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Authors and Affiliations

  1. 1.Department of Endocrinology and MetabolismZhongshan Hospital, Fudan UniversityShanghaiChina
  2. 2.Department of EndocrinologyJinshan Hospital, Fudan UniversityShanghaiChina
  3. 3.The Graduate School of Fujian Medical UniversityFuZhouChina

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