Circulating Levels of VEGF and CXCL1 Are Predictive of Metastatic Organotropismin in Patients with Colorectal Cancer

Abstract

Colorectal cancer is the most common cancer of the gastrointestinal system and has a marked preference to metastasize to distant organs. In this study, we investigated whether levels of circulating serum pro-angiogenic cytokine such as chemokine (C-X-C motif) ligand 1 (melanoma growth-stimulating activity, alpha; CXCL1) and vascular endothelial growth factor (VEGF) have a role in favoring the colonization of metastatic cells at preferential sites and determined their prognostic significance in a cohort of 103 patients with metastatic colorectal cancer. Importantly, we found that the presence of elevated circulating levels of VEGF and CXCL1 are predictive of liver and lung metastasis, respectively. Moreover, the presence of a high serum VEGF level represents a negative prognostic factor for patients with liver metastases, with a worse prognosis than patients with lung metastasis. This suggests an additional role for circulating cytokines as a predictive tool for cancer prognosis and diagnosis, as well as for assessment of tumor sensitivity to anticancer therapy.

Interaction between Tumor-Associated Dendritic Cells and Colon Cancer Cells Contributes to Tumor Progression via CXCL1

“…CXCL1 is upregulated in various cancers and associated with cancer progression, such as cancer cell growth, proliferation, tumor angiogenesis and metastasis, after the activation of CXCR2 [27,28,29]. In addition, CXCL1 is not only involved in cancer progression, but also responsible for resistance to several chemotherapeutic drugs, such as oxaliplatin, doxorubicin, and cyclophosphamide [30,31,32,33].…”

Chemokine (C-X-C motif) ligand 1 is associated with tumor progression and poor prognosis in patients with colorectal cancer

“…Chemokine (C-X-C motif) ligand 1 (CXCL1), also named GRO-α, is a member of the G protein-coupled receptor family that binds specifically to CXC chemokine receptor 2 [ 11 , 12 ]. CXCL1 is overexpressed in CRC and facilitates metastasis and progression [ 13–15 ]. However, the prognostic significance of CXCL1 overexpression and related underlying mechanisms are not fully understood.…”

“Vessels in the Storm”: Searching for Prognostic and Predictive Angiogenic Factors in Colorectal Cancer

“…Specifically, in a study conducted on seventy CRC patients, it was found that serum VEGF expression levels, determined by ELISA, were significantly correlated with advanced stage and metastases but not with age, gender, and tumor localization [ 14 ]. Another study, involving a cohort of one-hundred three CRC patients, reported that elevated circulating levels of VEGF were prognostic for liver and lung metastasis [ 104 ]. Kwon and colleagues have examined the expression levels of VEGF, IL-6 and C-Reactive Protein in patients who underwent curative resection for CRC and determined their reciprocal association and with histological findings.…”

“…Also, gene polymorphism in VEGF-A could hold prognostic information: a recent study demonstrated that the homozygous genotype VEGF-2578 AA had significant effect on time to tumor recurrence [ 106 ]. In order to strengthen the prognostic value of VEGF, some studies have suggested the parallel evaluation for circulating cytokines, including the chemokine, CXC motif, Ligand 1 (CXCL1), and IL-6 [ 104 ]. However, results from these studies were contradictory [ 105 ].…”