Development of a thyroid cancer prognostic model based on the mitophagy-associated differentially expressed genes

Abstract

Abstract Background The prevalence of thyroid cancer (ThyC), a frequent malignant tumor of the endocrine system, has been rapidly increasing over time. The mitophagy pathway is reported to play a critical role in ThyC onset and progression in many studies. This research aims to create a mitophagy-related survival prediction model for ThyC patients. Methods Genes connected to mitophagy were found in the GeneCards database. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provided information on the expression patterns of ThyC-related genes. To identify differentially expressed genes (DEGs), R software was employed. The prognostic significance of each DEG was assessed using the prognostic K-M curve. The prognostic model was built using LASSO, ROC, univariate, and multivariate Cox regression analyses. Finally, a nomogram model was developed to predict the survival outcome of ThyC patients in the clinical setting. Results Through differential analysis, functional enrichment analysis, and protein–protein interaction (PPI) network analysis, we screened 10 key genes related to mitophagy in ThyC. The risk model was eventually developed using LASSO and Cox regression analyses based on the six DEGs related to mitophagy. An altered expression level of a mitophagy-related prognostic gene, GGCT, was found to be the most significant one, according to the KM survival curve analysis. An immunohistochemical (IHC) investigation revealed that ThyC tissues expressed higher levels of GGCT than normal thyroid tissues. The ROC curve verified the satisfactory performance of the model in survival prediction. Multivariate Cox regression analysis showed that the pathological grade, residual tumor volume, and initial tumor lesion type were significantly linked to the prognosis. Finally, we created a nomogram to predict the overall survival rate of ThyC patients at 3-, 5-, and 7- year time points. Conclusion The nomogram risk prediction model was developed to precisely predict the survival rate of ThyC patients. The model was validated based on the most significant DEG GGCT gene expression in ThyC. This model may serve as a guide for the creation of precise treatment plans for ThyC patients.

Keywords

• Thyroid cancer
• Prognosis
• Mitophagy
• TCGA