Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Biosci Rep. 2021 Apr 30;41(4). doi: 10.1042/BSR20210337.
Studies have identified the methylation of N1 adenosine (m1A), an RNA modification, playing an important role in the progression of the tumorigenesis. The present study aimed to analyze the genetic characteristics and prognostic value of m1A regulators in pancreatic cancer. In the present study, data on gene mutations, single-nucleotide variants (SNVs), and copy number variation (CNV) were obtained from 363 patients with pancreatic cancer in the Cancer Genome Atlas (TCGA) database, and survival analysis was performed using the logarithmic rank test and Cox regression model. The chi-squared test was used to examine the relationship between the changes in m1A regulatory factors and clinicopathological characteristics. And we used ICGC database to verify the reliability of prognostic markers. The results show that changes in m1A-regulating genes are related to clinical stage and that the expression of some m1A-regulating genes is positively correlated with CNV. In addition, the low expression of the 'eraser' gene ALKBH1 is related to the poor prognosis of patients with pancreatic cancer, and its expression level has important clinical significance for patients with pancreatic adenocarcinoma (PAAD). Mechanistically, ALKBH1 may participate in the occurrence and development of pancreatic cancer through mTOR and ErbB signaling pathway. The expression of m1A-regulating genes can be used as a prognostic marker for pancreatic cancer. These findings provide valuable clues for us to understand the epigenetics of m1A in pancreatic cancer.
研究已经确定,RNA 修饰物 N1 腺苷的甲基化(m1A)在肿瘤发生的进展中起着重要作用。本研究旨在分析胰腺癌中 m1A 调节剂的遗传特征和预后价值。在本研究中,从癌症基因组图谱(TCGA)数据库中 363 名胰腺癌患者中获取了基因突变、单核苷酸变异(SNV)和拷贝数变异(CNV)的数据,并使用对数秩检验和 Cox 回归模型进行了生存分析。卡方检验用于检验 m1A 调节因子的变化与临床病理特征之间的关系。我们使用 ICGC 数据库来验证预后标志物的可靠性。结果表明,m1A 调节基因的变化与临床分期有关,并且一些 m1A 调节基因的表达与 CNV 呈正相关。此外,“擦除器”基因 ALKBH1 的低表达与胰腺癌患者的预后不良有关,其表达水平对胰腺腺癌(PAAD)患者具有重要的临床意义。从机制上讲,ALKBH1 可能通过 mTOR 和 ErbB 信号通路参与胰腺癌的发生和发展。m1A 调节基因的表达可以作为胰腺癌的预后标志物。这些发现为我们了解胰腺癌中 m1A 的表观遗传学提供了有价值的线索。