Role of Galectins in the Liver Diseases: A Systematic Review and Meta-Analysis

Yang An; Shixue Xu; Yiting Liu; Xiangbo Xu; Cyriac Abby Philips; Jiang Chen; Nahum Méndez-Sánchez; Xiaozhong Guo; Xingshun Qi

doi:10.3389/fmed.2021.744518

Role of Galectins in the Liver Diseases: A Systematic Review and Meta-Analysis

Front Med (Lausanne). 2021 Oct 27:8:744518. doi: 10.3389/fmed.2021.744518. eCollection 2021.

Authors

Yang An^{1

2}, Shixue Xu¹, Yiting Liu^{1

3}, Xiangbo Xu^{1

2}, Cyriac Abby Philips⁴, Jiang Chen¹, Nahum Méndez-Sánchez⁵, Xiaozhong Guo¹, Xingshun Qi¹

Affiliations

¹ Meta-Analysis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China.
² Postgraduate College, Shenyang Pharmaceutical University, Shenyang, China.
³ Department of Physical Examination Center, The First Affiliated Hospital, China Medical University, Shenyang, China.
⁴ The Liver Unit and Monarch Liver Laboratory, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi, India.
⁵ Liver Research Unit Medica Sur Clinic and Foundation and Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.

Abstract

Background: Galectins, a family of β-galactoside-binding proteins, are related to the development and progression of various human diseases such as cancer, heart failure, and chronic kidney disease. However, its role in liver diseases is unclear. Methods: The PubMed, Embase, and Cochrane Library databases were searched. Hazard ratios (HRs), odds ratios (ORs), and mean differences (MDs) with 95% CIs were pooled to evaluate the association of the galectins with the outcomes and risk of liver diseases by a random effects model. Results: Thirty three studies involving 43 cohorts and 4,168 patients with liver diseases were included. In the patients with hepatocellular carcinoma (HCC), high expression of galectin-1 and -3 in the tissues was significantly associated with worse overall survival (galectin-1: HR = 1.94, 95% CI = 1.61-2.34, p < 0.001; galectin-3: HR = 3.29, 95% CI = 1.62-6.68, p < 0.001) and positive vascular invasion (galectin-1: OR = 1.74, 95% CI = 1.18-2.58, p = 0.005; galectin-3: OR = 2.98, 95% CI = 1.58-5.60, p = 0.001); but, high expression of galectin-4 and -9 in the tissues was significantly associated with better overall survival (galectin-4: HR = 0.53, 95% CI = 0.36-0.79, p = 0.002; galectin-9: HR = 0.56, 95% CI = 0.44-0.71, p < 0.001) and negative vascular invasion (galectin-4: OR = 0.36, 95% CI = 0.19-0.72, p = 0.003; galectin-9: OR = 0.60, 95% CI = 0.37-0.97, p = 0.037). Serum galectin-3 level was significantly higher in HCC (MD = 3.06, 95% CI = 1.79-4.32, p < 0.001), liver failure (MD = 0.44, 95% CI = 0.23-0.66, p < 0.001), liver cirrhosis (MD = 1.83, 95% CI = 1.15-2.51, p < 0.001), and chronic active hepatitis B (MD = 18.95, 95% CI = 10.91-27.00, p < 0.001); serum galectin-9 level was significantly higher in HCC (MD = 3.74, 95% CI = 2.57-4.91, p < 0.001) and autoimmune hepatitis (MD = 8.80, 95% CI = 7.61-9.99, p < 0.001). Conclusion: High galectin-1 and -3 and low galectin-4 and -9 expression indicate worse outcomes of patients with HCC. Serum galectin-3 and -9 levels are positively associated with the risk of chronic liver diseases.

Keywords: cirrhosis; fibrosis; galectins; hepatitis; hepatocellular carcinoma.