Dataset Information

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

ABSTRACT: 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 from multiple medical 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.

SUBMITTER: Zhang J

PROVIDER: S-EPMC6082955 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Zhang Jun J Liu Xinyu X Yu Guanzhen G Liu Lei L Wang Jiejun J Chen Xiaoyu X Bian Yuhai Y Ji Yuan Y Zhou Xiaoyan X Chen Yinan Y Ji Jun J Xiang Zhen Z Guo Lei L Fang Jingyuan J Sun Yihong Y Cao Hui H Zhu Zhenggang Z Yu Yingyan Y

Frontiers in pharmacology 20180802

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 ...[more]

PMID: 30116193

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Project description:The present study compared the expression levels of limb-bud and heart (LBH) between gastric intestinal-type adenocarcinoma (GITA) and healthy gastric tissues; with the aim of investigating the possible effect of LBH on the prognosis of patients with GITA and to analyze the associated signaling pathways in GITA. Three Oncomine gastric datasets were utilized for the preliminary prediction of the expression levels of LBH mRNA in GITA and healthy gastric tissues. Gene expression and corresponding clinical data of 163 patients with GITA were downloaded from The Cancer Genome Atlas. Wilcoxon signed rank-sum test was used to distinguish the clinical value of LBH expression in the various clinicopathological features. Subsequently, Kaplan-Meier univariate and Cox multivariate survival analyses were performed to determine the prognostic significance of LBH expression in patients with GITA. Function enrichment analysis was conducted for the co-expression gene of LBH, defined as correlation coefficient r>0.06 and P<0.05 using Pearson's ?2 test. Bioinformatics data demonstrated that compared with that in the normal gastric mucosa, LBH mRNA expression was dramatically higher in GITA tissues (P<0.05). There were significant relationships between the differential expression levels of LBH and clinicopathological parameters in GITA patients (all p<0.05), including pathological stage T (T3-4 vs. T1-2), lymph node metastasis (no vs. yes), distant metastasis (no vs. yes), histological grade (grade 3 vs. grades 1-2) and tumor stage (stages 3-4 vs. stages 1-2). Additionally, the overall survival and disease-free survival (DFS) of patients in the high expression group were poorer compared with those in the low expression group (P<0.05). Cox multivariate survival analysis indicated that increased LBH expression was an independent predictor of poor DFS prognosis in patients with GITA (P=0.045). In summary, LBH is highly expressed in GITA, which can be used as an independent predictor of poor prognosis in patients with GITA. LBH co-expressed genes are closely associated with GITA tumor migration and metastasis.

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Dataset Information

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

Publications

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

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