Research Paper|Volume 15, Issue 5|pp 1668—1684

Identification and validation of eight estrogen-related genes for predicting prognosis of papillary thyroid cancer

Yu Zeng¹, Weike Ma¹, Lijuan Li², Gaojian Zhuang³, Guoqing Luo³, Hong Zhou³, Weijing Hao¹, Yu Liu¹, Fengli Guo¹, Mengran Tian^1,^4,⁶, Xianhui Ruan¹, Ming Gao^1,^4,⁵, Xiangqian Zheng¹

¹Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
²Department of Cancer Prevention Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
³The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan 511500, China
⁴Department of Thyroid and Breast Surgery, Tianjin Union Medical Center, Tianjin 300121, China
⁵Tianjin Key Laboratory of General Surgery in Construction, Tianjin Union Medical Center, Tianjin 300121, China
⁶School of Medicine, Nankai University, Tianjin 300071, China

* Equal contribution

Received: October 17, 2022Accepted: February 6, 2023Published: March 13, 2023

https://doi.org/10.18632/aging.204582

Copyright: © 2023 Zeng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Papillary thyroid cancer (PTC) is one of the most common malignant tumors in female, and estrogen can affect its progression. However, the targets and mechanisms of estrogen action in PTC remain unclear. Therefore, this study focuses on the relationship between estrogen-related genes (ERGs) expression and prognosis in PTC, particularly neuropeptide U (NMU), and its important role in tumor progression. Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, differentially expressed genes (DEGs) predominantly enriched in ERGs were identified between PTC and normal tissue. Then, we identified ERGs that contributed most to PTC prognosis, including Transducer of ERBB2 1 (TOB1), trefoil factor 1 (TFF1), phospholipase A and acyltransferase 3 (PLAAT3), NMU, kinesin family member 20A (KIF20A), DNA topoisomerase II alpha (TOP2A), tetraspanin 13 (TSPAN13), and carboxypeptidase E (CPE). In addition, we confirmed that NMU was highly expressed in PTC and explored the effect of NMU on PTC cells proliferation in vitro and in vivo. The results showed that the proliferative capacity of PTC cells was significantly reduced with NMU knockdown. Moreover, the phosphorylation levels of the Kirsten rat sarcoma virus (KRAS) signaling pathway were significantly lower with NMU knockdown. These results suggest that ERGs, especially NMU, may be novel prognostic indicators in PTC.