Citation: Yiqiu Hu, Xiujuan Hong, Zhijun Yuan, Jiayi Mu, Xiaoxiao Zhang, Zhihao Fang, Ying Yuan, Shu Zheng, Cheng Guo. Pan-cancer analysis of DNA epigenetic modifications by hydrophilic interaction liquid chromatography-tandem mass spectrometry[J]. Chinese Chemical Letters, ;2023, 34(7): 108023. doi: 10.1016/j.cclet.2022.108023 shu

Pan-cancer analysis of DNA epigenetic modifications by hydrophilic interaction liquid chromatography-tandem mass spectrometry

Yiqiu Hu ^{a, 1} ,
Xiujuan Hong ^{a, 1} ,
Zhijun Yuan ^{a, 1} ,
Jiayi Mu ^a ,
Xiaoxiao Zhang ^a ,
Zhihao Fang ^a ,
Ying Yuan ^{a, b} ,
Shu Zheng ^{a, b} ,
Cheng Guo ^{a, b, *,}

a.
Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
b.
Cancer Center, Zhejiang University, Hangzhou 310058, China

cheng_guo@zju.edu.cn

Received Date: 24 August 2022
Revised Date: 10 November 2022
Accepted Date: 24 November 2022
Available Online: 26 November 2022

Figures(4)

Accumulating evidence in recent years indicates that DNA methylation (5-methyl-2′-deoxycytidine, 5-mdC) and hydroxymethylation (5-hydroxymethyl-2′-deoxycytidine, 5-hmdC) have been implicated in various biological processes, and the aberrations of these DNA cytosine modifications is tightly associated with cancer. N⁶-methyl-2′-deoxyadenosine (m⁶dA), as a newly discovered epigenetic modification in genome of mammals, has been demonstrated to play vital regulatory roles in tumorigenesis. However, the content information of m⁶dA in human tumor tissues is still limited and pan-cancer analysis of these DNA epigenetic modifications is lacked. Herein, we developed a sensitive and robust stable isotope-diluted hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method for accurate quantification of m⁶dA, 5-mdC and 5-hmdC in genomic DNA from 82 pairs of human tumor tissues and matched tumor-adjacent normal tissues. The types of tumors included esophagus cancer, lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, stromal tumor and colorectal cancer. Compared to the normal tissues, we revealed the level of m⁶dA was increased in tumor tissues of esophagus cancer, lung cancer and liver cancer, whereas the level of m⁶dA was diminished in tumor tissues of pancreatic cancer and gastric cancer; while the contents of 5-mdC and 5-hmdC exhibited significant decrease in tumor tissues of most types of cancer. It is worth noting that we revealed, for the first time, the content of genomic m⁶dA in pancreatic cancer, stromal tumor and colorectal cancer. The significant changes of these DNA epigenetic modifications indicate they may serve as indicators of cancers. In addition, this study will benefit for better understanding of the regulatory roles of these DNA epigenetic modifications in cancers.
- HILIC-MS/MS,
- Pan-cancer analysis,
- N⁶-methyl-2′-deoxyadenosine,
- 5-Methyl-2′-deoxycytidine,
- 5-Hydroxymethyl-2′-deoxycytidine
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