The Scavenger Receptor MARCO Expressed by Tumor-Associated Macrophages Are Highly Associated With Poor Pancreatic Cancer Prognosis

Bian Shi; Junfeng Chu; Tao Huang; Xiaoqian Wang; Qiujian Li; Qilong Gao; Qingxin Xia; Suxia Luo

doi:10.3389/fonc.2021.771488

The Scavenger Receptor MARCO Expressed by Tumor-Associated Macrophages Are Highly Associated With Poor Pancreatic Cancer Prognosis

Front Oncol. 2021 Oct 29:11:771488. doi: 10.3389/fonc.2021.771488. eCollection 2021.

Authors

Bian Shi¹, Junfeng Chu², Tao Huang³, Xiaoqian Wang³, Qiujian Li¹, Qilong Gao¹, Qingxin Xia⁴, Suxia Luo²

Affiliations

¹ Department of Integrated Traditional Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
² Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
³ Department of Hepatopancreatobiliary Surgery, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
⁴ Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Macrophage-targeting therapies have become attractive strategies for immunotherapy. Deficiency of MARCO significantly inhibits tumor progression and metastasis in murine models of pancreatic cancer. However, the role of MARCO in patients with pancreatic cancer remains unclear. In the present study, we analyzed tumor-associated macrophage (TAM)-related changes using the Cancer Genome Atlas database. We observed a significant enrichment of M2 macrophages in pancreatic cancer tissues. We found that several pro-tumor markers are increased in cancer tissues, including CD163, CD206, SIRPα, LILRB1, SIGLEC10, AXL, MERTK, and MARCO. Crucially, MARCO is highly or exclusively expressed in pancreatic cancer across many types of solid tumors, suggesting its significant role in pancreatic cancer. Next, we investigated the expression of MARCO in relation to the macrophage marker CD163 in a treatment-naïve pancreatic cancer cohort after surgery (n = 65). MARCO and CD163 were analyzed using immunohistochemistry. We observed increased expression of CD163 and MARCO in pancreatic cancer tissues compared with paracancerous tissues. Furthermore, we observed a large variation in CD163 and MARCO expression in pancreatic cancer tissues among cases, suggesting the heterogeneous expression of these two markers among patients. Correlation to clinical data indicated a strong trend toward worse survival for patients with high CD163 and MARCO macrophage infiltration. Moreover, high CD163 and MARCO expression negatively affected the disease-free survival and overall survival rates of patients with pancreatic cancer. Univariate and multivariate analysis revealed that CD163 and MARCO expression was an independent indicator of pancreatic cancer prognosis. In conclusion, high CD163 and MARCO expression in cancer tissues is a negative prognostic marker for pancreatic cancer after surgery. Furthermore, anti-MARCO may be a novel therapy that is worth studying in depth.

Keywords: CD163; MARCO; pancreatic cancer; prognosis; tumor-associated macrophage.