Identification of PANoptosis-related genes as prognostic indicators of thyroid cancer.

Background: Thyroid cancer (THCA) has become a common malignancy in recent years, with the mortality rate steadily increasing. PANoptosis is a unique kind of programmed cell death (PCD), including pyroptosis, necroptosis, and apoptosis, and is involved in the proliferation and prognosis of numerous cancers. This paper demonstrated the connection between PANoptosis-related genes and THCA based on the analyses of Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, which have not been evaluated yet. Methods: We identified PANoptosis-related differentially expressed genes (PRDEGs) by multi-analyzing the TCGA-THCA and GEO datasets. To identify the significant PRDEGs, a prognostic model was constructed using least absolute shrinkage and selection operator regression (LASSO). The predictive values of the significant PRDEGs for THCA outcomes were determined using Cox regression analysis and nomograms. Gene enrichment analyses were performed. Finally, immunohistochemistry was carried out using the human protein atlas. Results: A LASSO regression model based on nine PRDEGs was constructed, and the prognostic value of key PRDEGs was explored via risk score. Univariate and multivariate Cox regression were implemented to identify further three significant PRDEGs closely related to distant metastasis, lymph node metastasis, and tumor stage. Then, a nomogram was constructed, which presented high predictive accuracy for 5 years survival of THCA patients. Gene enrichment analyses in THCA were strongly associated with PCD pathways. CASP6 presented significantly differential expression during clinical T stage, N stage, and PFI events (P < 0.05 for all) and demonstrated the highest degree of diagnostic efficacy in PRDEGs (HR: 2.060, 95 % CI: 1.170-3.628, P < 0.05). Immunohistochemistry showed CASP6 was more abundant in THCA tumor tissue. Conclusion: A potential prognostic role for PRDEGs in THCA was identified, providing a new direction for treatment. CASP6 may be a potential therapeutic target and a novel prognostic biomarker for THCA.