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

Abstract

Chemokine (C-X-C motif) ligand 1 (CXCL1) is a chemotactic cytokine known to regulate cancer progression and invasion. However, the prognostic significance of CXCL1 expression in colorectal cancer (CRC) has not been fully characterized. The present study explored the clinicopathological significance and potential role of CXCL1 in the carcinogenesis and progression of CRC. The protein expression of CXCL1 was measured immunohistochemically in tissue microarrays constructed from 276 CRC patients. CXCL1 expression levels and their associations with clinicopathological characteristics and patient survival were evaluated. The effect of CXCL1 on glycolysis was also examined. High CXCL1 expression was detected in 165 (59.8%) cases. CXCL1 expression was correlated with tumor diameter (P=0.002), T stage (P=0.044), N stage (P=0.005), M stage (P=0.001), lymphovascular invasion (P=0.010), and carcinoembryonic antigen status (P=0.019). High CXCL1 expression was validated as an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) by both univariate and multivariate Cox regression analyses (both P<0.05). Experimentally, expression of CXCL1 was knocked down by stable transfected short hairpin RNA, resulting in a significantly decreased rate of glycolysis both in in vitro assays and in patients’ samples (P<0.05). Silencing the expression of CXCL1 decreased the levels of the glycolytic enzymes GLUT1, HK2, and LDHA. In conclusion, by inducing glycolysis, CXCL1 plays a crucial role in both cancer progression and metastasis in CRC patients. The CXCL1 expression level is an independent prognostic factor for both OS and DFS. Moreover, CXCL1 may serve as a new biomarker and potential therapeutic target for CRC treatment.

XIAOPI formula inhibits the pre-metastatic niche formation in breast cancer via suppressing TAMs/CXCL1 signaling

“…Clinically, the tissue microarray analysis of 276 patients with colon cancer indicated that CXCL1 played a vital role in the progression and metastasis of colon cancer [44]. The expression level of CXCL1 is an independent prognostic factor for both OS and DFS in patients with colon cancer [45]. Therefore, disrupting the TAMs/CXCL1 signaling to block PMN formation is emerging as a promising therapeutic approach for cancer metastasis.…”

Chemokines and their Receptors: Multifaceted Roles in Cancer Progression and Potential Value as Cancer Prognostic Markers

“…CXCL1 has been reported to play an important role in CRC progression and metastasis by inducing glycolysis [179]. CXCL1 is also an ELR + CXC chemokine that induces angiogenesis by binding to CXCR2 [109].…”

Circ_0026344 restrains metastasis of human colorectal cancer cells via miR-183

“…An accumulating number of evidence shows that chemokines are frequently expressed in various tumours to regulate tumour cells function in both physiological and pathological conditions [2,3]. In terms of CRC, several chemokines are highly expressed in tumour tissue and cell line, like CXCL1 [4], CXCL8 [5], CXCL10 [6] and CCL20 [7]. Functional assays demonstrated that CXCL8 and CCL20 co-stimulation led to the increase of CRC cells proliferation and migration [8,9].…”