Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Validation the DNA Methylation Landscape of TFF1/TFF2 in Gastric Cancer

Ze Qian
ORCID logo ,
Yifan Jiang
,
Chunhui Shou
,
Jinghua Yu
,
Dongdong Huang
,
Haiyang Xie
,
Lin Zhou
,
Diyu Chen
* ,
Shusen Zheng
* ORCID logo
Version 1 : Received: 13 October 2022 / Approved: 20 October 2022 / Online: 20 October 2022 (11:07:15 CEST)

A peer-reviewed article of this Preprint also exists.

Qian, Z.; Jiang, Y.; Shou, C.; Yu, J.; Huang, D.; Xie, H.; Zhou, L.; Chen, D.; Zheng, S. Validation of the DNA Methylation Landscape of TFF1/TFF2 in Gastric Cancer. Cancers 2022, 14, 5474. Qian, Z.; Jiang, Y.; Shou, C.; Yu, J.; Huang, D.; Xie, H.; Zhou, L.; Chen, D.; Zheng, S. Validation of the DNA Methylation Landscape of TFF1/TFF2 in Gastric Cancer. Cancers 2022, 14, 5474.

Abstract

Gastric cancer (GC) is one of the most common malignancies around the world, and the incidence of GC is increasing in the past decades. In addition to genetic modifications, epigenetic alterations catalyzed by DNA methyltransferases (DNMTs) are a well-characterized epigenetic hallmark in gastric cancer. Nowadays, DNA methylation landscape is essential for maintaining the silence of tumor suppressor genes (TSGs). As an important group of peptide, TFF family has been confirmed to function as a TSG in various kinds of cancers. However, whether TFFs could be modified by DNA methylation in gastric cancer remains unknown. In this study, we initially screened out two expression profiles about GC from Gene Expression Omnibus (GEO) database. The higher expressions of TFF1 and TFF2 were observed in GC tumor tissues than normal tissues. Additionally, we illustrated that the expressions of TFF1/TFF2 were associated to the overall survival (OS) and tumor free survival (TFS) of GC patients via through the Kaplan-Meier analysis. Subsequently, the integrative analysis was performed to estimate the DNA methylation level of each site in TFF1/TFF2 CpG islands. Importantly, our findings indicated that hyper-methylation of cg01886855 and cg26403416 were separately responsible for the downregulation of TFF1 and TFF2 in GC samples. Besides, utilizing the gain of function assay, we demonstrated that TFF1/TFF2 could suppress the proliferation of GC cells. Based on these results, We identified that TFF1 and TFF2 acted as the putative tumor suppressors in gastric cancer, which suggested that TFFs could be two candidate biomarkers for predicting tumor recurrence in gastric cancer patients. Furthermore, these findings highlight a potential therapeutic approach in targeting the TFFs for the treatment of gastric cancer.

Keywords

gastric cancer; DNA methylation; TFF1; TFF2

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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