UBE2C Is a Potential Biomarker of Intestinal-Type Gastric Cancer With Chromosomal Instability
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-typ...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.00847/full |
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| author | Jun Zhang Xinyu Liu Guanzhen Yu Guanzhen Yu Lei Liu Jiejun Wang Xiaoyu Chen Yuhai Bian Yuan Ji Xiaoyan Zhou Yinan Chen Jun Ji Zhen Xiang Lei Guo Jingyuan Fang Yihong Sun Hui Cao Zhenggang Zhu Yingyan Yu |
| author_facet | Jun Zhang Xinyu Liu Guanzhen Yu Guanzhen Yu Lei Liu Jiejun Wang Xiaoyu Chen Yuhai Bian Yuan Ji Xiaoyan Zhou Yinan Chen Jun Ji Zhen Xiang Lei Guo Jingyuan Fang Yihong Sun Hui Cao Zhenggang Zhu Yingyan Yu |
| author_sort | Jun Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T19:31:33Z |
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| language | English |
| last_indexed | 2024-04-12T19:31:33Z |
| publishDate | 2018-08-01 |
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| spelling | doaj.art-0fce516898a84a8aaa68c599ed60f2492022-12-22T03:19:20ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-08-01910.3389/fphar.2018.00847395464UBE2C Is a Potential Biomarker of Intestinal-Type Gastric Cancer With Chromosomal InstabilityJun Zhang0Xinyu Liu1Guanzhen Yu2Guanzhen Yu3Lei Liu4Jiejun Wang5Xiaoyu Chen6Yuhai Bian7Yuan Ji8Xiaoyan Zhou9Yinan Chen10Jun Ji11Zhen Xiang12Lei Guo13Jingyuan Fang14Yihong Sun15Hui Cao16Zhenggang Zhu17Yingyan Yu18Department of Surgery, Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Surgery, Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaChangzheng Hospital, Affiliated to Second Military Medical University, Shanghai, ChinaDepartment of Oncology, Longhua Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Surgery, Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaChangzheng Hospital, Affiliated to Second Military Medical University, Shanghai, ChinaRenji Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaRenji Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaZhongshan Hospital, Affiliated to Fudan University, School of Medicine, Shanghai, ChinaCancer Hospital, Affiliated to Fudan University School of Medicine, Shanghai, ChinaDepartment of Surgery, Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Surgery, Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Surgery, Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Surgery, Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaRenji Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaZhongshan Hospital, Affiliated to Fudan University, School of Medicine, Shanghai, ChinaRenji Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Surgery, Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Surgery, Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThis 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.https://www.frontiersin.org/article/10.3389/fphar.2018.00847/fullgastric cancerLauren classificationdata miningbiomarkersUBE2C |
| spellingShingle | Jun Zhang Xinyu Liu Guanzhen Yu Guanzhen Yu Lei Liu Jiejun Wang Xiaoyu Chen Yuhai Bian Yuan Ji Xiaoyan Zhou Yinan Chen Jun Ji Zhen Xiang Lei Guo Jingyuan Fang Yihong Sun Hui Cao Zhenggang Zhu Yingyan Yu UBE2C Is a Potential Biomarker of Intestinal-Type Gastric Cancer With Chromosomal Instability Frontiers in Pharmacology gastric cancer Lauren classification data mining biomarkers UBE2C |
| title | UBE2C Is a Potential Biomarker of Intestinal-Type Gastric Cancer With Chromosomal Instability |
| title_full | UBE2C Is a Potential Biomarker of Intestinal-Type Gastric Cancer With Chromosomal Instability |
| title_fullStr | UBE2C Is a Potential Biomarker of Intestinal-Type Gastric Cancer With Chromosomal Instability |
| title_full_unstemmed | UBE2C Is a Potential Biomarker of Intestinal-Type Gastric Cancer With Chromosomal Instability |
| title_short | UBE2C Is a Potential Biomarker of Intestinal-Type Gastric Cancer With Chromosomal Instability |
| title_sort | ube2c is a potential biomarker of intestinal type gastric cancer with chromosomal instability |
| topic | gastric cancer Lauren classification data mining biomarkers UBE2C |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.00847/full |
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