Zhang Tao, Sheng Ping, Jiang Yuting
Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Department of General Surgery, The First People's Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan Province, China.
J Cancer Res Clin Oncol. 2023 Jul;149(7):2805-2822. doi: 10.1007/s00432-022-04150-7. Epub 2022 Jul 3.
N6 methyladenosine (m6A) RNA methylation regulators play a key role in the occurrence and development of many tumors. However, the function of N6 methyladenosine (m6A) RNA methylation regulators in pancreatic adenocarcinoma (PAAD) has not been fully clarified.
We used data set from GEPIA 2, UALCAN, TIMER, TISIDB, CBioPortal database to analyze the gene expression of 20 major m6A RNA methylation regulators.
Our study revealed that the irregularity of m6A regulators were associated with poor prognosis in PAAD. Meantime, 13 m6A regulators showed high expression in PAAD samples (ALKBH5, ELAVL1, FTO, HNRNPC, IGF2BP2, METTL14, METTL16 (METT10D), RBM15, VIRMA (KIAA1429), YTHDF1, YTHDF2, YTHDF3 and ZC3H13). In these regulators, we evaluated HNRNPC and IGF2BP2 were significantly correlated with worse outcomes and ALKBH5, IGF2BP2, METTL16 (METT10D), RBM15 were significantly correlated with PAAD in advanced stage. Moreover, we showed m6A regulators is correlated with Immuno-regulators' (Immunoinhibitors, Immunostimulators and MHC molecules) expression and levels of immune infiltration in PAAD. Bioinformatics further demonstrate m6A regulators were participated in revising in RNA processing.
Our study investigated that the m6A regulatory factors may serve as a biomarker and a potential target of immunotherapy for PAAD.
N6-甲基腺苷（m6A）RNA甲基化调节因子在许多肿瘤的发生发展中起关键作用。然而，N6-甲基腺苷（m6A）RNA甲基化调节因子在胰腺腺癌（PAAD）中的功能尚未完全阐明。
我们使用来自GEPIA 2、UALCAN、TIMER、TISIDB、CBioPortal数据库的数据集来分析20种主要m6A RNA甲基化调节因子的基因表达。
我们的研究表明，m6A调节因子的异常与PAAD的不良预后相关。同时，13种m6A调节因子在PAAD样本中高表达（ALKBH5、ELAVL1、FTO、HNRNPC、IGF2BP2、METTL14、METTL16（METT10D）、RBM15、VIRMA（KIAA1429）、YTHDF1、YTHDF2、YTHDF3和ZC3H13）。在这些调节因子中，我们评估了HNRNPC和IGF2BP2与较差的预后显著相关，而ALKBH5、IGF2BP2、METTL16（METT10D）、RBM15与晚期PAAD显著相关。此外，我们表明m6A调节因子与PAAD中免疫调节因子（免疫抑制剂、免疫刺激剂和MHC分子）的表达及免疫浸润水平相关。生物信息学进一步证明m6A调节因子参与RNA加工的调控。
我们的研究调查发现，m6A调节因子可能作为PAAD的生物标志物和免疫治疗的潜在靶点。
