Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2018; 24(19): 2120-2129
Published online May 21, 2018. doi: 10.3748/wjg.v24.i19.2120
Prognostic impact of the red cell distribution width in esophageal cancer patients: A systematic review and meta-analysis
Wei-Yu Xu, Xiao-Bo Yang, Wen-Qin Wang, Yi Bai, Jun-Yu Long, Jian-Zhen Lin, Jian-Ping Xiong, Yong-Chang Zheng, Xiao-Dong He, Hai-Tao Zhao, Xin-Ting Sang
Wei-Yu Xu, Xiao-Bo Yang, Yi Bai, Jun-Yu Long, Jian-Zhen Lin, Jian-Ping Xiong, Yong-Chang Zheng, Hai-Tao Zhao, Xin-Ting Sang, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Wen-Qin Wang, Xiao-Dong He, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Author contributions: Xu WY and Yang XB contributed equally to this work; Xu WY conceived, designed and wrote the manuscript that led to the submission; Xu WY, Yang XB and Wang WQ searched and filtered the literature; Long JY, Lin JZ and Xiong JP selected and interpreted the data; Wang WQ and Zheng YC revised the manuscript; Zhao HT and Sang XT provided financial support for this work; He XD, Zhao HT and Sang XT are co-corresponding authors, and they contributed equally to this work; All authors read and approved the final manuscript.
Supported by CAMS Innovation Fund for Medical Science (CIFMS), No. 2017-12M-4-003; International Science and Technology Cooperation Projects, No. 2015DFA30650 and No. 2016YFE0107100; Capital Special Research Project for Health Development, No. 2014-2-4012; and Beijing Natural Science Foundation, No. L172055.
Conflict-of-interest statement: The authors deny any conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and 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:
Correspondence to: Xin-Ting Sang, MD, Professor, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Wangfujing, Beijing 100730, China.
Telephone: +86-10-69156042 Fax: +86-10-69156042
Received: March 7, 2018
Peer-review started: March 7, 2018
First decision: March 21, 2018
Revised: April 3, 2018
Accepted: April 16, 2018
Article in press: April 15, 2018
Published online: May 21, 2018
Research background

Esophageal cancer (EC) was the eighth most common cancer globally, with about half of all cases occurring in China. Prominent symptoms usually do not appear until the cancer has infiltrated over 60% of the circumference of the esophageal tube, by which time the tumor is already in an advanced stage and the prognosis generally tends to be fairly poor. Therefore, finding a simple and effective prognostic indicator is particularly urgent for individualized treatment of EC patients. Recently, red blood cell distribution width (RDW), as an important complete blood count parameter which has a close correlation with cancer-related inflammation, has been investigated as an important prognostic factor for EC patients in more and more studies, but the conclusions of these studies have not been consistent. Therefore, we conducted this meta-analysis to explore and verify the real role of RDW in the prognosis of patients with EC.

Research motivation

We systematically reviewed the existing studies regarding the role of RDW in the prognosis of EC patients and performed a meta-analysis with the extracted data to clarify the real impact of RDW on the outcomes of the EC patients. Identifying the real role of RDW in the prognosis of patients with EC and the defects existing in the previous and current studies can guide the future researchers to conduct more well-designed related studies on this topic and the upstream or downstream research related to RDW.

Research objectives

The main objectives of this article were to perform a meta-analysis of the data provided in these studies with inconsistent conclusions about the prognostic effect of RDW on EC patients, and to verify the real impact of RDW on the prognosis of EC patients by increasing the sample size. In the end, we could determine whether we need to conduct further studies on this topic according to the conclusion of this systematic review and meta-analysis.

Research methods

First, we searched four related electronic databases (PubMed, EMBASE, Web of Science and Cochrane Library) using the identified MESH terms, and finally identified six studies which met the standards based on the inclusion and exclusion criteria of the selected literature, then we assessed the quality of the included studies according to Newcastle-Ottawa quality scale. Second, we used the electronic EXCEL table to collect the data from the included studies that we needed and utilized statistical software (STATA version 12.0) to conduct statistical analysis of the related data. Third, we performed the sensitivity analysis, subgroup analysis, Begg’s funnel plot and Egger’s linear regression test to explore the potential source of heterogeneity among studies, to find the influencing factors that affect the role of RDW in the prognosis of EC patients and point out the directions for further related research in the future.

Different from the traditional review, we used meta-analysis methods to synthesize data and perform statistical analysis to the relevant literature and quantify the effect of RDW on the prognosis of EC patients. Moreover, in addition to sensitivity analysis and subgroup analyses to find sources of heterogeneity, we also used the Begg’s funnel plot and Egger’s linear regression test to quantify publication bias rather than just using the traditional funnel plot for qualitative analysis. These were the characteristics and indicate the novelty of the research methods used in our study.

Research results

This systematic review and meta-analysis indicated that elevated RDW was not an independent risk factor for the worse outcome of EC patients overall, whether it’s for overall survival/cancer-specific survival [hazard ratio (HR) = 1.27, 95% confidence interval (CI): 0.97-1.57, P = 0.000] or disease-free survival (HR = 1.42, 95% CI: 0.96-1.88, P = 0.000). The prognostic value of RDW in patients with EC is only reflected in the retrospective study (HR = 1.42, 95%CI: 1.16-1.69, P = 0.000) of small samples (sample size ≤ 400, HR = 1.45, 95% CI = 1.13-1.76, P = 0.000) currently, and there is a need to choose the appropriate RDW cutoff value (RDW > 13%, HR = 1.45, 95%CI: 1.13-1.76, P = 0.000) as a prerequisite. Therefore, the actual effect of RDW on the prognosis of EC patients needs further prospective multicenter large-sample studies to be validated in the future.

Research conclusions

Different from the traditional viewpoints, our systematic and meta-analysis demonstrated that RDW had no correlation with the prognosis of EC patients, no matter favorable or unfavorable. Therefore, such traditional theories and assumptions, that cancer-related inflammation leads to an increased RDW in the blood, and elevated RDW in turn suggests the occurrence of cancer, were challenged and questioned by the results of our meta-analysis. At the same time, it also suggests that we could perform the meta-analysis to statistically analyze the inconsistent result data of different types of small-sample studies and achieve a conclusion that is completely different from our previous understanding. This leads to the emergence of new theories and assumptions and provides direction for our future research design and potential mechanism research. Our systematic reviews and meta-analysis suggest that we should be more cautious and rational to see the impact of increased RDW on the prognosis of EC patients in our future clinical work.

Research perspectives

From our study, we could learn that we can’t blindly believe in traditional ideas that already exist. When the opinions of previous studies are inconsistent and chaotic, we should use statistical methods to perform statistical clustering analysis on various data, and draw a scientific conclusion to guide our clinical work and indicate the future research direction. Moreover, through the systematic analysis of the previous research, we should carry out more multicenter, large-sample prospective studies in the future to overcome the defects of the current research in the study design to further verify the role of RDW in the prognosis of EC patients. In addition, we also need to conduct further basic experiments based on the results of such above-mentioned optimized research to uncover its underlying mechanisms.