Prognostic Signature: Immune Confrontation in the Papillary Thyroid Carcinoma Microenvironment

Background: Papillary thyroid carcinoma (PTC) is considered an inflammation-driven cancer. However, a systematic investigation of the relationship between the tumour immune microenvironment and prognosis in PTC has not been conducted. Methods: A prognostic model based on differentially expressed genes (DEGs) and progression-free survival (PFS) data from the Cancer Genome Atlas (TCGA) was established by least absolute shrinkage and selection operator (LASSO) and multivariate Cox analyses. 502 PTC cases were divided into low prognostic riskscore (PR) (L-PR) and high PR (H-PR) groups according to the median PR. We compared the immune characteristics between groups and verified these differences in validation cohorts. Furthermore, we explored cancer stem cells (CSCs) and tumour mutation burden (TMB) to explain the prognostic results. Findings: A prognostic signature (PR) based on 13 DEGs performed well in prognostic prediction (5-year area under the curve (AUC)= 0.861). The PR was positively correlated with age, stage, T classification, metastasis, RAS mutation, and subtypes as follicular or tall cell PTC. Importantly, the H-PR group, which had poor prognostic features, exhibited four main characteristics: comprehensive weakening of the immune system (immune escape) that was not observed in the L-PR group, a higher ratio of tumour-promoting immune cells, more CSCs, and a higher TMB than the L-PR group. Interpretation: Our prognostic model can effectively predict the prognosis and immune characteristics of PTC and revealed that immune escape, tumour-promoting immune infiltration patterns and tumour heterogeneity in the tumour microenvironment (TME) could be mechanisms of poor prognosis in PTC. Funding Statement: National Natural Science Foundation of China (81600602). Declaration of Interests: The authors stated: "None." Ethics Approval Statement: Not required.