Characterization of m6A methylation modifications and tumor microenvironment infiltration in thyroid cancer.

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy worldwide, and immunotherapy is a new cancer treatment that stimulates and enhances the natural ability of the immune system to fight cancer cells. The role of RNA N6-methyladenosine (m6A) related genes in these challenges has recently become a research hotspot, but he potential role of m6A modifications in tumor microenvironment (TME) cell infiltration remains unknown. PURPOSE: There is growing evidence that m6A plays a critical role in the regulation of gene expression by participating in important biological processes. A comprehensive analysis of the m6A regulator-mediated infiltration characteristics of the TME will help advance the understanding of immune regulation in thyroid tumors. METHODS: This study assessed m6A modification modes in 510 thyroid cancer samples from the Cancer Genome Atlas (TCGA) databases according to a comprehensive set of 24 m6A regulators. In this study, we analyzed the biological characteristics and m6A methylation modification patterns. Based on this, we constructed m6A signatures and analyzed m6A modification features in tumor somatic mutations and TCGA molecular subtypes. RESULTS: These modification modes were systematically linked to TME cell infiltration signatures. m6A modification patterns were comprehensively assessed and correlated with immune cell infiltration features in the TME. An unsupervised clustering approach was applied and three distinct m6A modification subtypes and three m6A-associated gene subtypes were identified. Additionally, three distinct m6A methylation modification modes were identified in the thyroid cancer samples. The TME profiles of the identified genetic subtypes were strongly congruent with the immuno-heat and immuno-cold phenotypes. CONCLUSIONS: The results revealed that m6A modifications play an integral role in the diversity and complexity of thyroid carcinomas. Evaluating the m6A modification patterns of individual tumors will create more efficient immunotherapeutic strategies. A comprehensive analysis of the role of TME in thyroid cancer provides a research idea for studying the effect of m6A epigenetics on thyroid tumors and their immune microenvironment.

A meta-analysis of the association between gout, serum uric acid level, and obstructive sleep apnea.

Previous epidemiological investigations have evaluated the association between gout, serum uric acid levels, and obstructive sleep apnea syndrome (OSAS), but with inconsistent results. We conducted this meta-analysis aiming at providing clear evidence about whether OSAS patients have higher serum uric acid levels and more susceptible to gout. Relevant studies were identified via electronic databases from inception to December 17, 2018. Study selection was conducted according to predesigned eligibility criteria, and two authors independently extracted data from included studies. The hazard ratio (HR) and weighted mean difference (WMD) and their corresponding 95% confidence interval (CI) were derived using random-effects models. We conducted meta-, heterogeneity, publication bias, sensitivity, and subgroup analyses. Eighteen studies, involving a total of 157,607 individuals (32,395 with OSAS, 125,212 without OSAS) and 12,262 gout cases, were included. Results show that serum uric acid levels are elevated in patients with OSAS (WMD = 52.25, 95% CI 36.16-64.33); OSAS did not reach statistical significance as a predictor of gout (but there was a trend, HR = 1.25, 95% CI 0.91-1.70) and that the association between OSAS and serum uric acid was quite robust. OSAS may be a potential risk factor for hyperuricemia and the development of gout and thus, effective OSAS therapy may present as a valuable preventive measure against gout. Still, it is vital to undertake clinical studies with better designing to corroborate these associations and shed new light on it.