Association of complement components with risk of colorectal cancer: A systematic review and meta-analysis

Xiao-Lin Zhu; Lu Zhang; Su-Xia Qi

doi:10.4251/wjgo.v16.i5.2168

Association of complement components with risk of colorectal cancer: A systematic review and meta-analysis

World J Gastrointest Oncol. 2024 May 15;16(5):2168-2180. doi: 10.4251/wjgo.v16.i5.2168.

Authors

Xiao-Lin Zhu¹, Lu Zhang², Su-Xia Qi³

Affiliations

¹ Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266071, Shandong Province, China.
² Department of Medical Administration, Qingdao Municipal Hospital, Qingdao 266071, Shandong Province, China.
³ Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266071, Shandong Province, China. qisuxia_0@163.com.

Abstract

Background: Complement components could contribute to the tumor microenvironment and the systemic immune response. Nevertheless, their role in colorectal cancer (CRC) remains a contentious subject.

Aim: To elucidate the relationship between complement components and CRC risk and clinical characteristics.

Methods: Searches were conducted in PubMed, the Cochrane Library, and the China National Knowledge Infrastructure database until June 1, 2023. We included cohort studies encompassing participants aged ≥ 18 years, investigating the association between complement components and CRC. The studies were of moderate quality or above, as determined by the Agency for Healthcare Research and Quality. The meta-analysis employed fixed-effects or random-effects models based on the I² test, utilizing risk ratio (RR) and their corresponding 95% confidence interval (CI) for outcomes. Sensitivity and subgroup analyses were performed to validate the robustness of the collective estimates and identify the source of heterogeneity.

Results: Data from 15 studies, comprising 1631 participants that met the inclusion criteria, were included in the meta-analysis. Our findings indicated that protein levels of cluster of differentiation 46 (CD46) (RR = 3.66, 95%CI: 1.75-7.64, P < 0.001), CD59 (RR = 2.86, 95%CI: 1.36-6.01, P = 0.005), and component 1 (C1) (RR = 5.88, 95%CI: 1.75-19.73, P = 0.004) and serum levels of C3 (standardized mean difference = 1.82, 95%CI: 0.06-3.58, P = 0.040) were significantly elevated in patients with CRC compared to healthy controls. Strong expression of CD55 or CD59 was associated with a higher incidence of lymph node metastasis, whereas strong CD46 expression correlated with a higher incidence of tumor differentiation compared to low CD46 expression (P < 0.05 for all). Although specific pooled results demonstrated notable heterogeneity, subgroup analyses pointed to regional differences as the primary source of inconsistency among the studies.

Conclusion: Our analysis underscores that increased levels of specific complement components are associated with a heightened risk of CRC, emphasizing the potential significance of monitoring elevated complement component levels.

Keywords: Colorectal cancer; Complement components; Lymph node metastasis; Meta-analysis; Systematic review.