Meta-Analysis
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2019; 11(10): 898-908
Published online Oct 15, 2019. doi: 10.4251/wjgo.v11.i10.898
Prognostic and pathological impact of tumor budding in gastric cancer: A systematic review and meta-analysis
Yi-Xian Guo, Zi-Zhen Zhang, Gang Zhao, En-Hao Zhao
Yi-Xian Guo, Zi-Zhen Zhang, Gang Zhao, En-Hao Zhao, Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China
Author contributions: Guo YX and Zhang ZZ designed the study and wrote the manuscript; Guo YX and Zhang ZZ conducted the literature search; Guo YX and Zhang ZZ collected and retrieved the data; Guo YX and Zhang ZZ analyzed the data; Zhao EH and Zhao G critically reviewed and revised the manuscript; Guo YX, Zhang ZZ and Zhao EH contributed equally to this work; and all authors proofed the manuscript.
Supported by Shanghai Shenkang Hospital Development Center Three-Year Action Plan for Difficult Diseases Precision Treatment Project, No. 16CR2022A; Pudong New Area Joint Research Project, No. PW2017D-1; Shanghai Shenkang Hospital Development Center Technology Joint Promotion Project, No. SHDC12016236; Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Training fund, No. PYMDT-003.
Conflict-of-interest statement: The authors declare that they have no competing interests.
PRISMA 2009 Checklist statement: The manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: En-Hao Zhao, PhD, Associate Professor, Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai 200120, China. microzhaoenhao@hotmail.com
Telephone: +86-21-68383731 Fax: +86-21-68383731
Received: March 12, 2019
Peer-review started: March 15, 2019
First decision: July 31, 2019
Revised: September 2, 2019
Accepted: September 13, 2019
Article in press: September 13, 2019
Published online: October 15, 2019
Abstract
BACKGROUND

Tumor budding, is a promising prognostic hallmark in many cancers, and can help us better assess the degree of malignancy in gastric cancer (GC) and in colorectal cancer. In the past few years, several articles on the relationship between tumor budding and GC have been published, but different results have been observed. As the relationship between tumor budding and GC remains controversial, we integrated the data from 7 eligible studies to conduct a systematic review and meta-analysis.

AIM

To systematically evaluate the prognostic and pathological impact of tumor budding in GC.

METHODS

Literature searches were conducted in the PubMed, Cochrane Library, EMBASE and Web of Science databases, and 7 cohort studies involving 2178 patients met our criteria and included in the analysis. The patients were divided into those with high-grade tumor budding and those with low-grade tumor budding, and the cut-off values for tumor budding varied across the included studies. The hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to estimate the impact of tumor budding on overall survival (OS) in GC patients. The odds ratios (ORs) with 95%CIs were used to determine the correlation between tumor budding and pathological parameters (tumor stage, tumor differentiation, lymphovascular invasion, lymph node metastasis) of GC.

RESULTS

Seven studies involving 2178 patients were included in the meta-analysis. The combined ORs suggested that high-grade tumor budding was significantly associated with tumor stage (OR = 6.63, 95%CI: 4.01-10.98, P < 0.01), tumor differentiation (OR = 3.74, 95%CI: 2.68-5.22, P < 0.01), lymphovascular invasion (OR = 7.85, 95%CI: 5.04-12.21, P < 0.01), and lymph node metastasis (OR = 5.75, 95%CI: 3.20-10.32, P < 0.01). Moreover, high-grade tumor budding predicted a poor 5-year OS (HR = 1.79, 95%CI: 1.53-2.05, P < 0.01) in patients with GC and an adverse 5-year OS (HR = 1.93, 95%CI: 1.45-2.42, P < 0.01) in patients with intestinal-type GC.

CONCLUSION

High-grade tumor budding suggested a poor prognosis in patients with GC or intestinal-type GC.

Keywords: Tumor budding, Gastric cancer, Intestinal-type gastric cancer, Epithelial-mesenchymal transition

Core tip: Tumor budding is known to be a specific pathological marker in the diagnosis of colorectal cancer and squamous cell carcinoma. However, the prognostic value of tumor budding in patients with gastric cancer (GC) has not been extensively studied and remains controversial. This is the first meta-analysis to evaluate the prognostic value of tumor budding in GC. The findings suggest that tumor budding is closely related to tumor stage, tumor differentiation, lymphovascular invasion and lymph node metastasis in GC.