Estrogen-related genes identified as novel prognostic indicators in papillary thyroid cancer

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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 the development of PTC. We first downloaded expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases for PTC and normal tissue and identified differentially expressed genes (DEGs), which were predominantly enriched for ERGs. Then, we identified ERGs that contributed most to PTC prognosis based on univariate Cox regression and Lasso Cox analysis. We filtered out 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 explored the effect of NMU on the proliferation of PTC cells by in vitro experiments, confirmed high NMU expression in PTC and 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.

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