UBE2C Is a Potential Biomarker of Intestinal-Type Gastric Cancer With Chromosomal Instability

被引：52

作者：

Zhang, Jun ^{[1
]}

Liu, Xinyu ^{[1
]}

Yu, Guanzhen ^{[2
,3
]}

Liu, Lei ^{[1
]}

Wang, Jiejun ^{[2
]}

Chen, Xiaoyu ^{[4
]}

Bian, Yuhai ^{[4
]}

Ji, Yuan ^{[5
]}

Zhou, Xiaoyan ^{[6
]}

Chen, Yinan ^{[1
]}

Ji, Jun ^{[1
]}

Xiang, Zhen ^{[1
]}

Guo, Lei ^{[1
]}

Fang, Jingyuan ^{[4
]}

Sun, Yihong ^{[5
]}

Cao, Hui ^{[4
]}

Zhu, Zhenggang ^{[1
]}

Yu, Yingyan ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Gastr Neoplasms, Dept Surg,Ruijin Hosp,Shanghai Inst Digest Surg, Shanghai, Peoples R China

[2] Second Mil Med Univ, Changzheng Hosp, Shanghai, Peoples R China

[3] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Dept Oncol, Shanghai, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai, Peoples R China

[5] Fudan Univ, Sch Med, Zhongshan Hosp, Shanghai, Peoples R China

[6] Fudan Univ, Sch Med, Canc Hosp, Shanghai, Peoples R China

来源：

FRONTIERS IN PHARMACOLOGY | 2018年 / 9卷

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

gastric cancer; Lauren classification; data mining; biomarkers; UBE2C; BREAST-CANCER; MICROARRAY DATA; LUNG-CANCER; EXPRESSION; PROGNOSIS; CARCINOMA; OVEREXPRESSION; CLASSIFICATION; IDENTIFICATION; PROLIFERATION;

D O I：

10.3389/fphar.2018.00847

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

This study explored potential biomarkers associated with Lauren classification of gastric cancer. We screened microarray datasets on gastric cancer with information of Lauren classification in gene expression omnibus (GEO) database, and compared differentially expressing genes between intestinal-type or diffuse-type gastric cancer. Four sets of microarray data (GSE2669, GSE2680, GDS3438, and GDS4007) were enrolled into analysis. By differential gene analysis, UBE2C, CDH1, CENPF, ERO1L, SCD, SOX9, CKS1B, SPP1, MMP11, and ANLN were identified as the top genes related to intestinal- type gastric cancer, and MGP, FXYD1, FAT4, SIPA1L2, MUC5AC, MMP15, RAB23, FBLN1, ANXA10, and ADH1B were genes related to diffuse- type gastric cancer. We comprehensively validated the biological functions of the intestinal- type gastric cancer related gene UBE2C and evaluated its clinical significance on 1,868 cases of gastric cancer tissues frommultiplemedical centers of Shanghai, China. The gain of copy number on 20q was found in 4 out of 5 intestinal- type cancer cell lines, and no similar copy number variation (CNV) was found in any diffuse- type cancer cell line. Interfering UBE2C expression inhibited cell proliferation, migration and invasion in vitro, and tumorigenesis in vivo. Knockdown of UBE2C resulted in G2/M blockage in intestinal- type gastric cancer cells. Overexpression of UBE2C activated ERK signal pathway and promoted cancer cell proliferation. U0126, an inhibitor of ERK signaling pathway reversed the oncogenic phenotypes caused by UBE2C. Moreover, overexpression of UBE2C was identified in human intestinal- type gastric cancer. Overexpression of UBE2C protein predicted poor clinical outcome. Taken together, we characterized a group of Lauren classification- associated biomarkers, and clarified biological functions of UBE2C, an intestinal- type gastric cancer associated gene. Overexpression of UBE2C resulted in chromosomal instability that disturbed cell cycle and led to poor prognosis of intestinal- type gastric cancer.

引用

页数：12

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