Identification and validation of a novel lymph node metastasis-related model for papillary thyroid carcinoma to predict the prognosis.

Background: Papillary thyroid carcinoma (PTC) is a common malignancy with a good prognosis, but lymph node metastasis (LNM) is associated with a poor prognosis for patients. This study aimed to construct an LNM-related risk model and identify hub genes that could predict the prognosis of PTC.

Methods: Gene expression and clinical information were obtained from The Cancer Genome Atlas (TCGA). Cox analysis was used to select hub genes and construct a risk model. The model was validated through receiver operator characteristic (ROC) curve. Nomogram was constructed for clinical application. Survival analysis was performed by the Kaplan-Meier (K-M) curve. Methylation of hub genes and drug sensitivity were calculated in Gene Set Cancer Analysis (GSCA). The expression levels of four hub genes and their effect on the malignant features of PTC were further validated through cell experiments.

Results: A risk model was constructed by four hub genes ATP2C2, CXCL5, IL11, and TREM1. ROC curve showed that the AUC of the risk model for PTC prognosis at 3-, 5-, and 10-year was 0.91, 0.88, and 0.92, respectively. The nomogram indicated that risk score was more important than some clinical characteristics. High-risk group exhibited lower immune infiltration levels. In PTC, four hub genes might function as oncogenes, but ATP2C2 was lowly expressed in tumors and patients with LNM. Additionally, ATP2C2 overexpression promoted PTC cell migration, invasion, and LNM-related protein expression levels, while knockdown of CXCL5, IL11, and TREM1 inhibited PTC cells' malignant features.

Conclusions: We constructed an LNM-related risk model based on four hub genes, and targeting these key genes can benefit patients from immunotherapy or chemotherapy.