Low MARCO Expression is Associated with Poor Survival in Patients with Hepatocellular Carcinoma Following Liver Transplantation

Qi Zhang,&ast; Yuxuan Wei,&ast; Yihu Li, Xingyuan Jiao Organ Transplant Center, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingyuan Jiao, Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China, Email jiaoxingyuan@hotmail.comBackground: Macrophage receptor with collagenous structure (MARCO) reportedly plays a crucial role in the occurrence and development of several cancers. However, the association between MARCO and the prognosis of hepatocellular carcinoma (HCC) post-liver transplantation remains poorly elucidated.Methods: We examined MARCO expression at mRNA and protein level in 145 HCC samples and adjacent nontumor tissues using quantitative reverse transcription PCR, Western blot and immunohistochemistry. Furthermore, we analyzed the correlation of MARCO expression with clinicopathologic features and prognosis.Results: We assessed the association between MARCO expression and clinicopathologic features and used the Cox proportional hazards regression model to explore the association between MARCO expression and clinical prognosis of patients with HCC post-liver transplantation. We observed that the expression of MARCO at mRNA and protein level in adjacent nontumor tissues was higher than that in the HCC tissues. Low MARCO expression in HCC tissues was correlated with higher alpha-fetoprotein levels, higher incidence of microvascular invasion, and a higher number of patients beyond Milan criteria. Kaplan–Meier survival curves showed that patients with HCC with low MARCO expression exhibited poor overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analysis revealed that MARCO expression was an independent prognostic factor for OS (hazard ratio [HR] 2.696, 95% confidence interval [CI] 1.335– 5.444, P=0.006) and DFS (HR 2.867, 95% CI 1.665– 4.936, P< 0.001) in patients with HCC post-liver transplantation. Based on immunofluorescence analysis, MARCO expression was primarily localized to macrophages and might be associated with M2-like macrophage polarization during HCC.Conclusion: MARCO expression was downregulated in HCC and associated with poor prognosis of patients with HCC post-liver transplantation. Moreover, it could be a potential prognostic marker and therapeutic target in post-liver transplantation HCC.Keywords: MARCO, hepatocellular carcinoma, liver transplantation, prognosis