CD163 as a Potential Biomarker in Colorectal Cancer for Tumor Microenvironment and Cancer Prognosis: A Swedish Study from Tissue Microarrays to Big Data Analyses

SIMPLE SUMMARY: Through the analysis of tissue microarray (TMA) samples from colorectal cancer (CRC) patients and bioinformatical analyses of public databases and our clinical dataset, this study identifies the different expressions of CD163 in various tissues, the presence of the receptor in TME, the interaction with other biological processes and a positive correlation between CD163 dysfunction and worse prognosis. Therefore, CD163 can be used as a new biomarker to predict patient prognosis. ABSTRACT: (1) Background: CD163, a specific macrophage receptor, affects the progression of malignant tumors. Unfortunately, the regulation and expression of CD163 are poorly understood. In this study, we determined the expressions of CD163 in TMA samples from CRC patients and combined them with patient data from several Swedish hospitals. (2) Methods: The expressions of CD163 in tissue samples from CRC patients were examined. After combining 472 CRC patients’ gene expression and 438 CRC patients’ clinical data with the TCGA database, 964 cases from the GEO database, and experimental expression data from 1247 Swedish CRC patients, we selected four genes (PCNA, LOX, BCL2, and CD163) and analyzed the tumor-infiltrating immune cells (TICs) and CRC prognosis. (3) Results: Based on histopathological TMA analysis, CD163 was strongly expressed in the stroma of both normal and cancer tissues, and the expressions in normal and cancer cells varied from negative to strong. The results from public databases show decreased expression of CD163 in cancer tissue compared to normal mucosa (|log FC| > 1 and FDR < 0.01), and it is a negative prognostic factor for CRC patients (p-value < 0.05). Through tumor microenvironment (TME) analysis, we found a potential influence of CD163 on immune cell infiltration. Furthermore, the enrichment analysis indicated the possible interaction with other proteins and biological pathways. (4) Conclusions: CD163 is expressed differently in CRC tissue and is a negative prognostic factor. Its expression is associated with the TME and tumor purity of CRC. Considering all results, CD163 has the potential to be a predictive biomarker in the investigation of CRC.