<i>Helicobacter pylori</i> associated aberrant methylation genes in blood leukocyte and gastric mucosa

Zhang, Yang; Chen, Duo; Zhang, Lian; Ma, Jun-Ling; Zhou, Tong; Li, Zhe-Xuan; Liu, Wei-Dong; You, Wei-Cheng; Pan, Kai-Feng

doi:10.7150/jca.64613

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J Cancer 2021; 12(24):7326-7333. doi:10.7150/jca.64613 This issue Cite

Research Paper

Helicobacter pylori associated aberrant methylation genes in blood leukocyte and gastric mucosa

Yang Zhang^1#, Duo Chen^1#, Lian Zhang¹, Jun-Ling Ma¹, Tong Zhou¹, Zhe-Xuan Li¹, Wei-Dong Liu², Wei-Cheng You¹, Kai-Feng Pan^1✉

1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
2. Linqu Public Health Bureau, Linqu, Shandong, 262600, People's Republic of China.
#These authors contributed equally to this work.

✉ Corresponding authors: Kai-Feng Pan, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fucheng Rd, Haidian District, More

Citation:

Zhang Y, Chen D, Zhang L, Ma JL, Zhou T, Li ZX, Liu WD, You WC, Pan KF. Helicobacter pylori associated aberrant methylation genes in blood leukocyte and gastric mucosa. J Cancer 2021; 12(24):7326-7333. doi:10.7150/jca.64613. https://www.jcancer.org/v12p7326.htm

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Abstract

Background and Aim: Methylation alterations may be involved in Helicobacter pylori-associated gastric carcinogenesis. This study aims to explore the potential H.pylori-associated methylation biomarkers in blood leukocyte and gastric mucosa.

Methods: Five candidate H.pylori-associated aberrant methylation genes were selected from the previous genome-wide profiling panels and validated in blood leukocyte and gastric mucosa in multi-stages (case-control validation between H.pylori positive and negative subjects and self-control validation before and after anti-H.pylori treatment).

Results: GNAS methylation level was decreased in blood leukocyte (62.07% v.s. 46.33%, p<0.001) and gastric mucosa (56.30% v.s. 32.42%, p<0.001) of H.pylori positive subjects compared to negative controls. While, MTERF1 methylation level was increased significantly in blood leukocyte (29.57% v.s. 56.02%, p<0.001) and gastric mucosa (31.10% v.s. 47.50%, p<0.001) of positive subjects compared to controls. After successful H.pylori eradication, the methylation levels were increased from 44.87% to 60.88% (p<0.001) for GNAS and decreased from 46.19% to 34.56% (p<0.001) for MTERF1 in blood leukocyte. Similar increasing and decreasing methylation alterations were also found for the two genes after successful eradication in paired gastric mucosa. In TCGA database, an inverse relationship was found between GNAS methylation and mRNA expression (r=-0.12, p=0.027). The GC cases with higher GNAS expression levels showed significantly worse survival (HR, 2.09, 95%CI, 1.22-3.57, p=0.007) compared to lower expression subjects.

Conclusions: GNAS and MTERF1 methylation levels may be affected by H.pylori infection in gastric mucosa and blood leukocyte. GNAS may be involved in advanced stage of GC development, although the possible mechanism still needs further study in precancerous lesions.

Keywords: Gastric cancer, Helicobacter pylori, Methylation biomarker, Blood leukocyte, Gastric mucosa

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APA

Zhang, Y., Chen, D., Zhang, L., Ma, J.L., Zhou, T., Li, Z.X., Liu, W.D., You, W.C., Pan, K.F. (2021). Helicobacter pylori associated aberrant methylation genes in blood leukocyte and gastric mucosa. Journal of Cancer, 12(24), 7326-7333. https://doi.org/10.7150/jca.64613.

ACS

Zhang, Y.; Chen, D.; Zhang, L.; Ma, J.L.; Zhou, T.; Li, Z.X.; Liu, W.D.; You, W.C.; Pan, K.F. Helicobacter pylori associated aberrant methylation genes in blood leukocyte and gastric mucosa. J. Cancer 2021, 12 (24), 7326-7333. DOI: 10.7150/jca.64613.

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CSE

Zhang Y, Chen D, Zhang L, Ma JL, Zhou T, Li ZX, Liu WD, You WC, Pan KF. 2021. Helicobacter pylori associated aberrant methylation genes in blood leukocyte and gastric mucosa. J Cancer. 12(24):7326-7333.

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