Abstract
BackgroundThe incidence of thyroid cancer (THCA) continues to increase in recent decades. Accumulating evidence showed that the unbalanced alternative splicing (AS) promotes the occurrence of cancers and leads to poor prognosis of patients. However, the research on alternative splicing events in THCA is lacking, and its underlying mechanism is not fully understood. This study identifies a novel prognostic signature based on AS events to reveal the relationship of AS with tumor immune microenvironment.MethodsBased on the AS data, transcriptional data, and clinical information, the differentially expressed alternative splicings (DEASs) were screened out. Least absolute shrinkage and selection operator (LASSO) regression and multi-Cox regression analyses were employed to identify prognostic results related to AS events and establish a prognostic signature. The predictive ability of the signature was assessed by Kaplan-Meier (K-M) survival curve, risk plots, and receiver operating characteristic (ROC) curves. Furthermore, correlations between tumor-infiltrating immune cells, immune checkpoints, immune score and prognostic signature were analyzed.ResultsAccording to the LASSO regression analysis, a total of five AS events were selected to construct the signature. K-M survival curve showed that the higher the risk score, the worse the OS of the patients. Risk plots further confirmed this result. ROC curves indicated the high predictive efficiency of the prognostic signature. As for tumor immune microenvironment, patients in the high-risk group had a higher proportion of immune cells, including plasma cell, CD8+ T cell, macrophages (M0 and M2), and activated dendritic cell. Immune checkpoint proteins, such as PDCD1LG2, HAVCR2, CD274, etc., were significantly higher in the high-risk group. We also found that the ESTIMATE score, stromal score, and immune score were lower in the high-risk group, while the result of tumor purity was the opposite.ConclusionsCollectively, a prognostic signature consisting of five AS events in THCA was established. Furthermore, there was an inextricable correlation between immune cell infiltration, immune checkpoint proteins, and AS events. This study will provide a basis for THCA immunotherapy in the future.
Highlights
The incidence of thyroid cancer (THCA) continues to increase worldwide, mainly due to the progress of imaging technology and the increase of examination methods
A total of 506 THCA patients from The Cancer Genome Atlas (TCGA) database were enrolled in the study, and 11 of them were excluded for null splicing data, which were over 30%
We found that some common DEASs were detected in THCA, colorectal cancer, and head and neck squamous cell carcinoma, indicating that some alternative splicing (AS) events were ubiquitous in the occurrence and development in different types of cancers [20, 21]
Summary
The incidence of THCA continues to increase worldwide, mainly due to the progress of imaging technology and the increase of examination methods. The number of thyroid cancer cases detected in the USA each year increased by 240% from 1973 to 2002, eventually reaching 7.7 per 100,000 people. The mechanisms of THCA are complex because they are controlled by genetic alterations in gene mutation, increased copy number of genes and abnormal methylation of genes, which lead to heterogeneity of the disease [2, 3]. Doctors need to find new treatments as the traditional antineoplastic therapy did not achieve satisfactory results for all thyroid cancers [4]. The incidence of thyroid cancer (THCA) continues to increase in recent decades. The research on alternative splicing events in THCA is lacking, and its underlying mechanism is not fully understood. This study identifies a novel prognostic signature based on AS events to reveal the relationship of AS with tumor immune microenvironment
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