The SUMO E3 ligase CBX4 is identified as a poor prognostic marker of gastric cancer through multipronged OMIC analyses

Yi Pan; Qingshang Li; Zhijun Cao; Shuliang Zhao

doi:10.1016/j.gendis.2020.08.010

The SUMO E3 ligase CBX4 is identified as a poor prognostic marker of gastric cancer through multipronged OMIC analyses

Genes Dis. 2020 Sep 1;8(6):827-837. doi: 10.1016/j.gendis.2020.08.010. eCollection 2021 Nov.

Authors

Yi Pan¹, Qingshang Li¹, Zhijun Cao¹, Shuliang Zhao¹

Affiliation

¹ Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, PR China.

Abstract

Gastric cancer (GC) is one of the most common malignancies, with an ever-increasing incidence and high mortality rate. Chromobox4 (CBX4), also named hPC2, is a small ubiquitin-related modifier (SUMO) E3 ligase. Previous studies have found that high CBX4 expression is associated with tumor size, pathologic differentiation and decreased patient survival in hepatocellular carcinoma (HCC). However, the expression and prognostic value of CBX4 in GC have not been clarified. In our study, ONCOMINE, UALCAN, Kaplan-Meier Plotter, cBioPortal, DAVID 6.8 and TIMER were utilized. RT-PCR, immunohistochemistry (IHC), Western blot, CCK-8 assay, cell apoptosis assay, cell cycle assay were used to further verify in GC tissue samples or cell line. The transcriptional and protein level of CBX4 in GC tissues was found significantly elevated and a significant association between the expression of CBX4 and clinicopathological parameters was found in GC patients. Low expression of CBX4 in GC patients were correlated with a significantly improved prognosis. The functions of CBX4 are primarily related to the stem cell pluripotency signaling pathway, Hippo signaling pathway, HTLV-I infection, Notch signaling pathway, and N-glycan biosynthesis. Our results may provide novel insights for the selection of therapeutic targets and prognostic biomarkers for GC.

Keywords: Bioinformatics analysis; Chromobox4 (CBX4); Gastric cancer; Prognostic biomarker; Therapeutic target.