Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Despite significant improvements in therapeutic techniques for treating CRC, clinical outcomes in patients with advanced CRC remain poor, with local recurrence and metastasis being the major causes of cancer-related deaths [1], [2], [3]. Studies investigating molecular and biochemical changes in CRC indicate that recurrence and metastasis of CRC are complex processes caused by mutations that alter the functions of proto-oncogenes and tumor suppressor genes, resulting in deregulated proliferation, inhibition of apoptosis, epithelial-mesenchymal transition (EMT), promotion of angiogenesis and lymphangiogenesis, and escape of immune surveillance [4], [5], [6].

Cluster of differentiation 47 (CD47), also known as integrin-associated protein, is a transmembrane protein broadly expressed on the surface of various cell types. CD47 plays significant roles in many cellular functions such as proliferation, apoptosis, migration, and immune homeostasis. CD47 binds to signal regulatory protein alpha (SIRPα) on immune cells, such as macrophages and antigen-presenting cells, to initiate a signaling cascade that suppresses or inhibits phagocytosis by immune cells [7], [8], [9], [10]. Previously, CD47 has been reported to be overexpressed in various human cancers and has been associated with tumor development, progression, and poor prognosis [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]. Also, CD47 is associated with several phenotypic changes that favor carcinogenesis, including cell cycle, DNA repair, apoptosis, proliferation, angiogenesis, invasion, and EMT in many human cancers [7], [8], [9], [10].

Previously, CD47 overexpression was associated with enhanced proliferation, migration, invasion, EMT, angiogenesis, and apoptosis [21], [22], [23], [24], [25], as well as poor survival in CRC patients [21], [22], [23], [24], [26]. CD47 overexpression induced CRC cell migration and metastasis via tumor-associated macrophages [27]. Overexpression of CD47 also inhibited phagocytosis of CRC cells by macrophages and contributed to cancer immune evasion [28]. Treatment with an anti-CD47 antibody reduced tumor growth by enabling macrophages to phagocytize the cancer cells and initiated an antitumor cytotoxic T-cell immune response, suggesting the possibility of a novel therapeutic target for CRC [28], [29]. However, there has been no study on the oncogenic phenotypic changes associated with CD47 in human CRC samples.

This study aimed to analyze the expression of CD47 in human samples to determine whether CD47 expression affected the oncogenic behavior of CRC, including apoptosis, proliferation, angiogenesis, and lymphangiogenesis. We also investigated the prognostic value of CD47 expression in patients with CRC.