Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Aug 6, 2019; 7(15): 1954-1963
Published online Aug 6, 2019. doi: 10.12998/wjcc.v7.i15.1954
Vestigial like family member 3 is a novel prognostic biomarker for gastric cancer
Li-Hua Zhang, Zhuo Wang, Long-Hai Li, Yan-Kui Liu, Lin-Fang Jin, Xiao-Wei Qi, Chun Zhang, Teng Wang, Dong Hua
Li-Hua Zhang, Dong Hua, School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, Jiangsu Province, China
Li-Hua Zhang, Teng Wang, Dong Hua, Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu Province, China
Zhuo Wang, Department of Geriatrics, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, Jiangsu Province, China
Long-Hai Li, Chun Zhang, Wuxi Medical College, Jiangnan University, Wuxi 214122, Jiangsu Province, China
Yan-Kui Liu, Lin-Fang Jin, Xiao-Wei Qi, Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu Province, China
Author contributions: Zhang LH and Wang Z contributed equally to this work; Wang T and Hua D designed the research; Li LH, Liu YK, Jin LF, Qi XW, and Zhang C performed the research; Wang T and Hua D contributed new reagents and analytic tools; Li LH, Zhang LH, and Wang Z analyzed the data; Zhang LH and Wang Z wrote the paper.
Supported by the Natural Science Foundation of Jiangsu Province, No. BK20171150; the National Natural Science Foundation of China, No. 81502042; Research Project of Health and Family Planning Commission of Wuxi, No. Q201758; and Nanchang Hongda Jianghua Educational Foundation.
Institutional review board statement: This study was reviewed and approved by Affiliated Hospital of Jiangnan University Institutional Review Board.
Informed consent statement: Any personal item or information will not be published without explicit consent from the involved persons.
Conflict-of-interest statement: The authors report no conflicts of interest in this work.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Dong Hua, MD, PhD, Chief Doctor, Professor, Department of Oncology, Affiliated Hospital of Jiangnan University, No. 200, Huihe Road, Wuxi 214062, Jiangsu Province, China. wx89211@163.com
Telephone: +86-510-88682109 Fax: +86-510-85808820
Received: March 22, 2019
Peer-review started: March 22, 2019
First decision: May 13, 2019
Revised: June 22, 2019
Accepted: July 3, 2019
Article in press: July 3, 2019
Published online: August 6, 2019
Abstract
BACKGROUND

Vestigial like family member 3 (VGLL3) is associated with the prognosis of epithelial ovarian cancer and soft tissue sarcoma, but its role in gastric cancer (GC) is unclear.

AIM

To explore the expression pattern and clinical significance of VGLL3 in GC.

METHODS

Integrative analysis was performed on the GC transcriptome profiles and survival information deposited in the ONCOMINE, GEPIA, and ONCOLNC databases. The expression levels of VGLL3 mRNA and protein were analyzed in the freshly resected tumor and normal gastric tissues from GC patients by quantitative RT-PCR and Western blot, respectively. In addition, the in situ expression of VGLL3 in the GC tissues was determined by immunohistochemistry (IHC), and the patients were accordingly classified into the high and low expression groups. The correlation of VGLL3 expression status with patient prognosis was then determined by univariate and multivariate Cox regression analyses.

RESULTS

Analysis of the ONCOMINE and GEPIA databases showed that VGLL3 was significantly up-regulated in GC tissues (P = 0.003), and associated with the tumor TNM stage (P = 0.0163). The high VGLL3 expression group had a significantly worse prognosis compared to the low expression group, as per both GEPIA (P = 0.0057) and ONCOLNC (P = 0.01). The bioinformatics results were validated by the significantly higher VGLL3 mRNA and protein levels in the GC tissues compared to the adjacent normal tissues (P < 0.001) in a cohort of 30 GC patients. Furthermore, high in situ expression of VGLL3 protein was associated with more advanced N and TNM stages and HER2 mutation (P < 0.05) in a cohort of 172 patients. Kaplan-Meier analysis showed that the high VGLL3 expression group had a worse prognosis compared to the low expression group (P = 0.019). Multivariate analysis showed that VGLL3 expression status was an independent risk factor for prognosis. In addition, the prognostic risk model nomogram showed that VGLL3 was the most important indicator, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.613 for 3-year survival and 0.706 for 5-year survival. Finally, the protein interaction network analysis revealed that VGLL3 is likely involved in the Hippo signaling pathway.

CONCLUSION

VGLL3 is overexpressed in GC tissues and associated with a poor prognosis, indicating its potential as a novel prognosis biomarker and therapeutic target for GC.

Keywords: Vestigial like family member 3, Stomach adenocarcinoma, HER2 mutation, Gastric cancer, Bioinformatics analysis

Core tip: The present study for the first time revealed the expression of vestigial like family member 3 (VGLL3) in gastric cancer (GC) and its correlation with HER2 mutation. Overall, the findings of the present study suggest that VGLL3 is a novel prognostic biomarker for GC and highlight the significance of VGLL3 as a promising therapeutic target for GC.