Research Paper Volume 15, Issue 5 pp 1668—1684
Identification and validation of eight estrogen-related genes for predicting prognosis of papillary thyroid cancer
- 1 Department 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
- 2 Department 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
- 3 The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan 511500, China
- 4 Department of Thyroid and Breast Surgery, Tianjin Union Medical Center, Tianjin 300121, China
- 5 Tianjin Key Laboratory of General Surgery in Construction, Tianjin Union Medical Center, Tianjin 300121, China
- 6 School of Medicine, Nankai University, Tianjin 300071, China
Received: October 17, 2022 Accepted: February 6, 2023 Published: March 13, 2023
https://doi.org/10.18632/aging.204582How to Cite
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.
Abbreviations
TC: Thyroid cancer; PTC: Papillary thyroid cancer; ER: Estrogen receptor; ERGs: Estrogen-related genes; NMU: Neuropeptide U; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; DEGs: Differentially expressed genes; UCSC: University of California-Santa Cruz; TOB1: Transducer of ERBB2 1; TFF1: Trefoil factor 1; PLAAT3: Phospholipase A and acyltransferase 3; KIF20A: Kinesin family member 20A; TOP2A: DNA topoisomerase II alpha; TSPAN13: Tetraspanin 13; CPE: Carboxypeptidase E; OS: Overall survival; ROC: Receiver operating characteristic; AUC: Area under the curve; PFI: Progression-free interval; GSEA: Gene Set Enrichment Analysis; HR: Hazard ratio; IL6: Interleukin 6; JAK: Janus kinase 2; STAT3: Signal transducer and activator of transcription 3; IL2: Interleukin 2; STAT5: Signal transducer and activator of transcription 5; KRAS: Kirsten rat sarcoma virus; mTOR: mammalian-targeted rapamycin.