Overexpression of YEATS4 contributes to malignant outcomes in gastric carcinoma

American Journal of Cancer Research

Keiji Nishibeppu¹  Taisuke Imamura²  Jun Kiuchi³  Shuhei Komatsu⁴ 

[1] Department of Basic Pathology, National Defense Medical College, Tokorozawa, Japan;Department of Pathology, National Cancer Center Hospital, Tokyo, Japan;Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kawaramachihirokoji, Kamigyo-Ku, Kyoto, Japan;First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan

关键词: YEATS4;    overexpression;    gastric cancer;    TP53;    chemosensitivity;   

DOI  :  

学科分类：肿瘤学

来源: e-Century Publishing Corporation

【 摘 要 】

YEATS domain containing 4 (YEATS4) has functions of chromatin modification and transcriptional regulation and is in a gene-amplified region (12q13) in various human cancers. In this study, we tested whether YEATS4 acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). We analyzed 5 GC cell lines and 135 primary tumor samples of GC, which were curatively resected in our hospital. Overexpression of the YEATS4 protein was frequently detected in GC cell lines (5/5 cell lines, 100%) and primary GC tumor tissues (32/135 cases, 23.7%). Knockdown of YEATS4 inhibited proliferation, migration and invasion of GC cells through NOTCH2 down-regulation in a TP53 mutation-independent manner, and induced apoptosis in wild-type TP53 GC cells. Moreover, knockdown of YEATS4 improved chemosensitivity for CDDP and L-OHP. Overexpression of YEATS4 protein significantly correlated with more aggressive lymphatic invasion, larger tumor size, deeper tumor depth, positive lymph node metastasis and recurrence. Patients with YEATS4-overexpressing tumors had a lower overall survival rate than those with non-expressing tumors. Multivariate analysis demonstrated that YEATS4 was independently associated with poor outcomes. These findings suggest that YEATS4 plays a pivotal role in tumor malignant potential through its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.

【 授权许可】

CC BY-NC