A Novel Pyroptosis-Related Gene Signature for Prediction of Disease-Free Survival in Papillary Thyroid Carcinoma

Abstract

Background: The incidence and recurrence rate of papillary thyroid carcinoma (PTC) are high. Thus, it is critical to accurately identify patients at high risk of recurrence. Pyroptosis is a type of programmed cell death closely related to the progression and prognosis of cancer. However, the role of pyroptosis in PTC remains unclear. Methods: Transcriptome data for PTC patients were obtained from The Cancer Genome Atlas database. The expression level of pyroptosis-related genes (PRGs) in PTC and normal tissues was identified. Based on these differentially expressed genes, a risk score model of disease-free survival (DFS) was established using least absolute shrinkage and selection operator Cox regression. In-cluster and quantitative real-time PCR validations were carried out. A nomogram, in combination with clinical factors, was also established. In addition, its relationship with immune characteristics and tumor gene mutations is discussed. Results: A risk score model with four PRGs, including CASP6, CASP9, IL-18, and NOD1, was established. The samples were divided into high- and low-risk clusters, according to the risk score, revealing significant differences in DFS between the two clusters. A nomogram was established combining age, lymph node metastasis and extrathyroidal extension. The area under the curve (AUC) of predicting one-, five-, and 10-year DFS in PTC patients was 0.745, 0.801, and 0.803, respectively. The low-risk cluster showed higher levels of immune infiltration and immune checkpoint gene expression, while the high-risk cluster demonstrated a higher tumor mutation burden. Conclusion: A predictive DFS model was established, based on PRGs, which may aid in identifying patients at high risk of recurrence. The present study helps to better understand the role of pyroptosis in the progression and prognosis of PTC.

The Role of IL-18 in P2RX7-Mediated Antitumor Immunity

“…Levels of IL-18 and IFN-γ were shown to be lower in plasmas of non-small cell lung cancer patients [126] and in tumor tissue of colon cancer, melanoma, thyroid and esophageal cancer patients compared to those of healthy subjects, and low levels of IL-18 correlated with the presence of metastases, a poor outcome [127][128][129][130][131] and increased risk of developing acute myeloid leukemia [132]. Moreover, IL-18 levels were shown to be correlated with higher CD8+ T cells, NK cells infiltration and activity in colorectal cancer [133], melanoma [129] and thyroid carcinoma [130]. Accordingly, functional intratumoral CD8+ T cells were shown to express high levels of IL-18R in non-small cell lung cancer patients and were, furthermore, cytotoxic in the presence of IL-18 [126].…”