CD163 as a Biomarker in Colorectal Cancer: The Expression on Circulating Monocytes and Tumor-Associated Macrophages, and the Soluble Form in the Blood.

Daniëlle Krijgsman,Morten N Andersen,Rob A.E.M Tollenaar,Peter J.K Kuppen,Anni Skovbo,Holger J Møller,Marianne Hokland,Natasja L De Vries

doi:10.3390/ijms21165925

Abstract

The macrophage-associated molecule CD163 has been reported as a prognostic biomarker in different cancer types, but its role in colorectal cancer (CRC) is unclear. We studied CD163 in the tumor microenvironment and circulation of patients with CRC in relation to clinicopathological parameters. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum sCD163 levels and multiparameter flow cytometry was used to study the peripheral blood monocytes and their CD163 expression in CRC patients (N = 78) and healthy donors (N = 50). The distribution of tumor-associated macrophages (TAMs) was studied in primary colorectal tumors with multiplex immunofluorescence. We showed that CRC patients with above-median sCD163 level had a shorter overall survival (OS, p = 0.035) as well as disease-free survival (DFS, p = 0.005). The above-median sCD163 remained significantly associated with a shorter DFS in the multivariate analysis (p = 0.049). Moreover, a shorter OS was observed in CRC patients with an above-median total monocyte percentage (p = 0.007). The number and phenotype of the stromal and intraepithelial TAMs in colorectal tumors were not associated with clinical outcome. In conclusion, sCD163 and monocytes in the circulation may be potential prognostic biomarkers in CRC patients, whereas TAMs in the tumor showed no association with clinical outcome. Thus, our results emphasize the importance of the innate systemic immune response in CRC disease progression.

Highlights

Colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths worldwide [1]
We investigated CD163 expressed by circulating monocytes and tumor-associated macrophages (TAMs), and its soluble circulating form in relation to the clinicopathological parameters in CRC
We evaluated the levels of Soluble CD163 (sCD163) in serum and observed no differences between healthy donors and CRC patients, which is in agreement with studies on ovarian cancer [13], melanoma [14], and multiple myeloma [17], but in contrast with a study on hepatocellular carcinoma [15] and another study in CRC patients by Ding et al [16]

Summary

Introduction

Colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths worldwide [1]. 25% of CRC patients have distant metastases at diagnosis [2]. Up to 25% of the patients diagnosed in the early stages eventually relapse or develop distant metastases following radical surgery and adjuvant chemotherapy [2,3]. In order to optimize treatment strategies, it is crucial that biomarkers are identified that associate with clinical outcome. Due to its critical role in combating tumor development and progression, the immune system has become an important focus in biomarker research. Studies have indicated important roles for monocytes and macrophages in CRC development and progression [4]

Methods

Results

Conclusion