Wang Xingquan, Su Dewang, Wei Yaqing, Liu Shilin, Gao Shengyu, Tian Hao, Wei Weiwei
Department of General Surgery, First Affiliated Hospital of Jiamusi University, Jiamusi, China.
Department of Infectious Diseases, City Center Hospital of Jiamusi City, Jiamusi, China.
Gland Surg. 2023 Jan 1;12(1):39-53. doi: 10.21037/gs-22-678. Epub 2023 Jan 6.
Although the prognosis of thyroid cancer (THCA) is generally good, many patients have a high risk of recurrence after treatment. N6-methyladenosine (m6A)-related long noncoding RNAs (lncRNAs) have been extensively studied in recent years. However, the potential of m6A-related lncRNAs to predict recurrence in THCA is unknown.
RNA sequencing (RNA-seq) data and clinical information for THCA were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs (DELs) were identified using the R package DESeq2. A coexpression network based on m6A-related genes and lncRNAs was constructed. The CIBERSORT algorithm and gene set enrichment analysis (GSEA) were used for immune-infiltrating cell estimation and clustering functional enrichment analysis, respectively. A Kaplan-Meier plot was used for prognostic analysis based on m6A-associated lncRNA risk patterns. The expression of lncRNAs in recurrent and nonrecurrent THCA tissues was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR).
A network of m6A-related lncRNAs containing 8 lncRNAs was constructed with good predictive power for recurrence in THCA. A total of 3 clusters were obtained, and cluster 1 was most associated with THCA recurrence. We found significantly lower levels of CD8 T cells and follicular helper T cells, and significantly higher levels of dendritic cells (DCs), M2 macrophages, resting DCs, regulatory T cells, and mast cells in cluster 1 patients. Pathway analysis revealed significant enrichment in natural killer cell-mediated cytotoxicity, butyrate metabolism, and cell adhesion molecules in cluster 1. The m6A-related lncRNA risk model was effective in predicting progression-free survival (PFS) in patients with THCA recurrence. RT-qPCR analysis based on 40 THCA clinical samples from our center found the risk model to be a good predictor of recurrence in THCA patients.
In summary, m6A-related lncRNAs may provide a novel predictive method for prognostic relapse in THCA patients.
尽管甲状腺癌（THCA）的预后总体良好，但许多患者在治疗后仍有较高的复发风险。近年来，N6-甲基腺苷（m6A）相关的长链非编码RNA（lncRNA）已得到广泛研究。然而，m6A相关lncRNA预测THCA复发的潜力尚不清楚。
从癌症基因组图谱（TCGA）下载THCA的RNA测序（RNA-seq）数据和临床信息。使用R包DESeq2鉴定差异表达的lncRNA（DEL）。构建基于m6A相关基因和lncRNA的共表达网络。分别使用CIBERSORT算法和基因集富集分析（GSEA）进行免疫浸润细胞估计和聚类功能富集分析。基于m6A相关lncRNA风险模式，使用Kaplan-Meier图进行预后分析。通过实时定量聚合酶链反应（RT-qPCR）分析lncRNA在复发性和非复发性THCA组织中的表达。
构建了一个包含8个lncRNA的m6A相关lncRNA网络，对THCA复发具有良好的预测能力。共获得3个聚类，聚类1与THCA复发最相关。我们发现聚类1患者中CD8 T细胞和滤泡辅助性T细胞水平显著降低，而树突状细胞（DC）、M2巨噬细胞、静息DC、调节性T细胞和肥大细胞水平显著升高。通路分析显示聚类1中自然杀伤细胞介导的细胞毒性、丁酸代谢和细胞粘附分子显著富集。m6A相关lncRNA风险模型可有效预测THCA复发患者的无进展生存期（PFS）。基于本中心40例THCA临床样本的RT-qPCR分析发现，该风险模型是THCA患者复发的良好预测指标。
总之，m6A相关lncRNA可能为THCA患者的预后复发提供一种新的预测方法。
