Abstract
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 microenvironment (TME) of PTC. Three subgroups (clusters 1, 2, and 3) were identified by consensus clustering of 19 prognosis-related m6A-lncRNA regulators, of which cluster 1 is preferentially related to 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 showed a worse prognosis, and the ROC indicated a reliable prediction performance for patients with PTC (AUC = 0.802). As expected, the immune scores, the infiltration levels of immune cells, and ESTIMATE scores in the low-risk subgroups were notably higher (p < 0.001) when compared with those in high-risk subgroups. Furthermore, GSEA analysis revealed 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. In addition, 30 clinical samples and different PTC cells were validated. This is the first study to reveal that m6A-lncRNAs plays 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.
Highlights
In the past few decades, the incidence of thyroid cancer has sharply increased globally (Lim et al, 2017)
These results indicated that m6A-long non-coding RNAs (lncRNAs) regulators are reliable factors for predicting prognosis
The molecular pathogenesis and development of papillary thyroid carcinoma (PTC) have been attributed to various factors, including the abnormal expression of tumor suppressor genes and oncogenes, exposure to external radiation, and genetic mutations. m6A RNA methylation is a nascent field of research but is garnering considerable scientific attention
Summary
In the past few decades, the incidence of thyroid cancer has sharply increased globally (Lim et al, 2017). Papillary thyroid carcinoma (PTC) is the most common histological subtype, accounting for up to 85% of all cases (Wang W. et al, 2020). Most patients with PTC usually present with indolent tumors and show a favorable prognosis after receiving standardized treatment. Up to 20–30% of patients with PTC experience recurrence or distant metastasis during follow-up (Wang W. et al, 2021; Sugino et al, 2020). Early detection and accurate management of the disease are vital for improving the prognosis. The underlying molecular mechanisms that regulate PTC progression remain unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
