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一种新型 m6A 相关预后标志物,用于预测肝细胞癌患者的总生存期。

A novel m6A-related prognostic signature for predicting the overall survival of hepatocellular carcinoma patients.

机构信息

Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China.

Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, China.

出版信息

IET Syst Biol. 2022 Feb;16(1):1-17. doi: 10.1049/syb2.12036. Epub 2021 Oct 14.

Abstract

Liver hepatocellular carcinoma (LIHC) comprises most cases of liver cancer with a poor prognosis. N -methyladenosine (m6A) plays important biological functions in cancers. Thus, the present research was aimed to determine biomarkers of m6A regulators that could effectively predict the prognosis of LIHC patients. Based on the data collected from the Cancer Genome Atlas (TCGA) database, the correlation between the mRNA expression levels and copy number variation (CNV) patterns were determined. Higher mRNA expression resulted from the increasing number of 9 genes. Using the univariate Cox regression analysis, 11 m6A regulators that had close correlations with the LIHC prognosis were identified. In addition, under the support of the multivariate Cox regression models and the least absolute shrinkage and selection operator, a 4-gene (YTHDF2, IGF2BP3, KIAA1429, and ALKBH5) signature of m6A regulators was constructed. This signature was expected to present a prognostic value in LIHC (log-rank test p value < 0.0001). The GSE76427 (n = 94) and ICGC-LIRI-JP (n = 212) datasets were used to validate the prognostic signature, suggesting strong power to predict patients' prognosis for LIHC. To sum up, genetic alterations in m6A regulatory genes were identified as reliable and effective biomarkers for predicting the prognosis of LIHC patients.

摘要

肝细胞癌(LIHC)构成了大多数肝癌病例,预后不良。N-甲基腺苷(m6A)在癌症中发挥着重要的生物学功能。因此,本研究旨在确定m6A 调节因子的生物标志物,这些标志物可以有效预测 LIHC 患者的预后。基于从癌症基因组图谱(TCGA)数据库中收集的数据,确定了 mRNA 表达水平与拷贝数变异(CNV)模式之间的相关性。随着 9 个基因数量的增加,mRNA 表达水平升高。使用单变量 Cox 回归分析,确定了 11 个与 LIHC 预后密切相关的 m6A 调节剂。此外,在多变量 Cox 回归模型和最小绝对收缩和选择算子的支持下,构建了一个 m6A 调节剂的 4 基因(YTHDF2、IGF2BP3、KIAA1429 和 ALKBH5)特征。该特征有望在 LIHC 中呈现预后价值(对数秩检验 p 值<0.0001)。使用 GSE76427(n=94)和 ICGC-LIRI-JP(n=212)数据集验证了预后特征,表明其具有预测 LIHC 患者预后的强大能力。总之,m6A 调节基因的遗传改变被鉴定为预测 LIHC 患者预后的可靠和有效生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2897/8849219/4ecbb1762c91/SYB2-16-1-g003.jpg

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