甲状腺乳头状癌中与m6A甲基化相关的长链非编码RNA的预后意义及潜在机制分析

Analysis of the prognostic significance and potential mechanisms of lncRNAs associated with m6A methylation in papillary thyroid carcinoma.

作者信息

Huang Yinde, Li Xin, Chen Wenbin, He Yuzhen, Wu Song, Li Xinyang, Hou Bingchen, Wang Shiyue, He Yuchen, Jiang Han, Lun Yu, Zhang Jian

机构信息

Department of Vascular and Thyroid Surgery, The First Hospital, China Medical University, Shenyang, Liaoning 110001, China.

出版信息

Int Immunopharmacol. 2021 Dec;101(Pt B):108286. doi: 10.1016/j.intimp.2021.108286. Epub 2021 Nov 1.

DOI:10.1016/j.intimp.2021.108286

PMID:34735975

Abstract

BACKGROUND

m6A methylation-related long non-coding RNAs (lncRNAs) play a significant role in the progression of various tumors and can be used as prognostic markers. However, whether m6A-related lncRNAs also play the same function as prognostic markers in papillary thyroid carcinoma (PTC) remains unclear.

METHODS

Consensus cluster analysis was performed to divide PTC samples obtained from The Cancer Genome Atlas database into two clusters according to the expression of m6A-related lncRNAs. Then, the least absolute shrinkage and selection operator (LASSO) regression analysis was performed to create and verify a prognostic model. Furthermore, the relationship among risk scores, clusters, programmed death-ligand 1 (PD-L1), tumor microenvironment (TME), clinicopathological characteristics, immune infiltration, immune checkpoint, and tumor mutation burden (TMB) was analyzed. In addition, a nomogram was created, and subsequently, the drug sensitivity of lncRNAs in the prognostic model was analyzed. Finally, the relationship between these lncRNAs and prognosis in pan-cancer was investigated.

RESULTS

The prognosis, RAS, BRAF, M, and TME were found to be different in two clusters. The prognostic model included three lncRNAs: PSMG3-AS1, BHLHE40-AS1, and AC016747.3. The risk score was associated with clusters, PD-L1, tumor microenvironment, clinicopathological characteristics, immune cell infiltration, immune checkpoint, and TMB, and thus, risk score was confirmed as useful prognostic indicator. Differentially expressed lncRNAs are involved in many malignancies and can be identified as cancer prognostic makers.

CONCLUSION

According to our research, we can regard m6A-related lncRNAs involved in the procession of PTC as a biomarker of progression-free survival for PTC patients, and pan-cancer.

摘要

背景

N6-甲基腺嘌呤（m6A）甲基化相关的长链非编码RNA（lncRNA）在多种肿瘤进展中起重要作用，可作为预后标志物。然而，m6A相关lncRNA在甲状腺乳头状癌（PTC）中是否也作为预后标志物发挥相同功能仍不清楚。

方法

进行一致性聚类分析，根据m6A相关lncRNA的表达将从癌症基因组图谱数据库获得的PTC样本分为两个聚类。然后，进行最小绝对收缩和选择算子（LASSO）回归分析以创建和验证预后模型。此外，分析了风险评分、聚类、程序性死亡配体1（PD-L1）、肿瘤微环境（TME）、临床病理特征、免疫浸润、免疫检查点和肿瘤突变负荷（TMB）之间的关系。另外，创建了列线图，随后分析了预后模型中lncRNA的药物敏感性。最后，研究了这些lncRNA与泛癌预后之间的关系。

结果

发现两个聚类中的预后、RAS、BRAF、M和TME不同。预后模型包括三个lncRNA：PSMG3-AS1、BHLHE40-AS1和AC016747.3。风险评分与聚类、PD-L1、肿瘤微环境、临床病理特征、免疫细胞浸润、免疫检查点和TMB相关，因此，风险评分被确认为有用的预后指标。差异表达的lncRNA参与许多恶性肿瘤，可被鉴定为癌症预后标志物。