The role of m6A RNA methylation-related lncRNAs in the prognosis and tumor immune microenvironment of papillary thyroid carcinoma

Abstract

Background: Emerging evidence has indicated that N6-methylandenosine (m6A) RNA methylation plays a critical role in cancer development. However, the function of m6A RNA methylation-related long noncoding RNAs (m6A-lncRNAs) in papillary thyroid carcinoma (PTC) has never been reported. This study aimed to investigate the role of m6A-lncRNAs in the prognosis and tumor immune microenvironment of PTC.Methods: The gene expression data of lncRNAs and 20 m6A methylation regulators with corresponding clinicopathological information download from the Cancer Genome Atlas database. Based on consensus clustering analysis, LASSO Cox regression, nivariate and multivariate Cox regression analysis were used to determine the role of m6A-lncRNA in the prognosis and tumor immune microenvironment of PTC.Results: Three subgroups (clusters 1, 2, and 3) were identified by consensus clustering of 19 prognosis-related m6A-lncRNA regulators，of which cluster 1 preferentially related with unfavorable prognosis, lower immune scores, and distinct immune infiltrate level. A risk-score model was established based on 8 prognosis-related m6A-lncRNAs. Patients with a high-risk score had a worse prognosis and the ROC indicated a reliable prediction performance for patients with PTC (AUC=0.802). As expected, the immune scores, infiltration levels of immune cells and ESTIMATE scores in the low-risk subgroups were notably higher (p < 0.001) compared with those of high-risk subgroups. Furthermore, GSEA analysis showed that tumor associated pathways, hallmarks, and biological processes were remarkably enriched in the high-risk subgroup. Further analysis indicated that the risk score and age were independent prognostic factors for PTC. An integrated nomogram was constructed that accurately predicted the survival status (AUC = 0.963). Moreover, a lncRNA–miRNA–mRNA regulated network was established based on seven prognosis-related m6A-lncRNAs. Additional, 30 clinical samples and different PTC cells were validated. Conclusions: This is the first study to reveal that m6A-lncRNAs play a vital role in the prognosis and TME of PTC. To a certain degree, m6A-lncRNAs can be considered as new, promising prognostic biomarkers and treatment targets.

A Potential Four-Gene Signature and Nomogram for Predicting the Overall Survival of Papillary Thyroid Cancer

“…A number of prior studies have proposed that combining BRAF, TERT, and RAS mutations with TNM staging can lead to better prediction of the prognosis of PTC patients [11][12][13]. Our team has previously constructed an integrated nomogram based on clinicopathological factors and the related risk scores, which showed significantly better predictive performance than AJCC stage [14][15][16].…”

Comprehensive analysis of lncRNA-mediated ceRNA regulatory networks and key genes associated with papillary thyroid cancer coexistent with Hashimoto’s thyroiditis

“…Long noncoding RNAs (lncRNAs) represent a group of transcripts with > 200 nucleotides and have been characterized as crucial regulators of biological processes and tumorigenesis by control of various key cellular genes. Recent studies have established that lncRNAs, such as m6A RNA methylation-related lncRNAs and differentiation-related lncRNAs are deregulated in PTC [11,12]. An increasing number of microRNAs (miRNAs) with less than 200 nucleotides were found to be abnormally expressed in human thyroid cancer and involved in the development of tumor biology [13,14].…”