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TCGA数据库中结直肠癌的DNA甲基化基因标志物

DNA-methylated gene markers for colorectal cancer in TCGA database.

作者信息

Zhang Hui, Sun Xun, Lu Ya, Wu Jianzhong, Feng Jifeng

机构信息

Research Center for Clinical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu 210000, P.R. China.

出版信息

Exp Ther Med. 2020 Apr;19(4):3042-3050. doi: 10.3892/etm.2020.8565. Epub 2020 Feb 27.

DOI:10.3892/etm.2020.8565
PMID:32256791
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7086203/
Abstract

Colorectal cancer (CRC) is characterized by the accumulation of genetic and epigenetic alterations in neoplastic processes. DNA methylation, as an important epigenetic process, contributes to the development of CRC. In the present study, the epigenetic landscape of genes in CRC was characterized by analyzing the dataset from The Cancer Genome Atlas database and 177 DNA-methylated genes were screened based on the criterion of the Pearson correlation (R) between expression and methylation levels being >0.4. Pathway enrichment analysis revealed prominent pathways, including transcription and metabolism, further implying their significant role in tumorigenesis. Among the methylated genes, only zinc finger protein (ZNF)726 with aberrant expression was determined to affect overall survival (OS) as well as disease-free survival of patients with CRC. In addition, ZNF726 was identified as an independent prognostic risk factor for OS in patients with CRC. The methylation-based regulation of ZNF726 expression in CRC cells was further assessed using the Cancer Cell Line Encyclopedia database. Finally, the CpG island methylation of the ZNF726 promoter was evaluated to further elucidate its role in the development of CRC. In conclusion, the epigenetic landscape of genes in terms of promoter methylation in CRC was characterized, revealing that aberrant expression of ZNF726 may be an independent prognostic risk factor for OS in patients with CRC.

摘要

结直肠癌（CRC）的特征是在肿瘤形成过程中积累遗传和表观遗传改变。DNA甲基化作为一种重要的表观遗传过程，促进了结直肠癌的发展。在本研究中，通过分析来自癌症基因组图谱数据库的数据来描绘结直肠癌中基因的表观遗传图谱，并基于表达水平与甲基化水平之间的皮尔逊相关系数（R）>0.4的标准筛选出177个DNA甲基化基因。通路富集分析揭示了包括转录和代谢在内的显著通路，进一步暗示了它们在肿瘤发生中的重要作用。在甲基化基因中，只有表达异常的锌指蛋白（ZNF）726被确定会影响结直肠癌患者的总生存期（OS）以及无病生存期。此外，ZNF726被确定为结直肠癌患者OS的独立预后危险因素。使用癌细胞系百科全书数据库进一步评估了结直肠癌细胞中ZNF726表达的甲基化调控。最后，评估了ZNF726启动子的CpG岛甲基化，以进一步阐明其在结直肠癌发展中的作用。总之，描绘了结直肠癌中基因启动子甲基化方面的表观遗传图谱，揭示ZNF726的异常表达可能是结直肠癌患者OS的独立预后危险因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d2/7086203/3a5d135c88a9/etm-19-04-3042-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d2/7086203/ee24e15b5eac/etm-19-04-3042-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d2/7086203/192a331975fa/etm-19-04-3042-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d2/7086203/631d8f7b922d/etm-19-04-3042-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d2/7086203/758c17b89da2/etm-19-04-3042-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d2/7086203/6cfaf2e2422a/etm-19-04-3042-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d2/7086203/7d7364d4dbde/etm-19-04-3042-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d2/7086203/3a5d135c88a9/etm-19-04-3042-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d2/7086203/ee24e15b5eac/etm-19-04-3042-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d2/7086203/192a331975fa/etm-19-04-3042-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d2/7086203/631d8f7b922d/etm-19-04-3042-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d2/7086203/758c17b89da2/etm-19-04-3042-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d2/7086203/6cfaf2e2422a/etm-19-04-3042-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d2/7086203/7d7364d4dbde/etm-19-04-3042-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d2/7086203/3a5d135c88a9/etm-19-04-3042-g06.jpg

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