Meta-analysis

PubMed, Web of Science, BIOSIS, and SciFinder were used to search the literature up to March 14, 2022. The following search phrases were entered: (Colorectal or rectal or colon or rectum) and (REG4 or REG IV) and (cancer or carcinoma or adenocarcinoma). No limitations on language or publication year were placed on the search. Inclusion criteria for studies were: (1) Studies that used immunohistochemistry to detect changes in REG4 expression in CRC; and (2) studies that used immunohistochemistry to relate REG4 expression to pathobiological behavior and CRC prognosis. Exclusion criteria included: (1) Abstracts, comments, reviews and meeting reports; (2) duplication of previous publications; (3) western blotting, RT–PCR, cDNA microarray, or transcriptomic sequencing for REG4 expression; and (4) lack of sufficient information. Two reviewers (Zhang CY and Zheng HC) independently gathered data from all relevant articles and evaluated the quality of the included studies using the Newcastle-Ottawa Scale (http://www.ohri.ca/programs/clinicalepidemiology/oxford.htm). For survival analysis, we extracted data from Kaplan-Meier curves using an Engauge Digitizer program. We calculated the hazard ratios (HRs) and accompanying 95% confidence intervals (CIs). Twelve papers regarding the correlation between REG4 expression and cancer risk, and clinicopathological or prognostic factors of CRC were found in PubMed, Web of Science, BIOSIS Citation Index, SciFinder, and CNKI (Supplementary Table 2). Samples of normal colorectal mucosa were only included in four papers[3,29-31]. In 12 investigations, a comparison was made between REG4 expression and the clinicopathological features of CRC[3,15,17,29-37]. Finally, we covered the importance of REG4 expression for prognosis in five papers [15,17,30,35,36].