Published online May 21, 2018. doi: 10.3748/wjg.v24.i19.2120
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
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.
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.
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.
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.
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.
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.
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.