Clinicopathologic Significance of CXCL12 and CXCR4 Expressions in Patients with Colorectal Cancer

Abstract

Background Colorectal cancer (CRC) is both a global and national burden, being the third most common malignancy in men and the second in women, worldwide. The prognosis of CRC is affected by various factors like the histological grade, angiolymphatic invasion, and distant metastases. Metastasis is an intricate process; one of the possible mechanisms is through the interaction of the chemokines CXCL12 and CXCR4. This study aims to reveal the expression patterns of CXCL12 and CXCR4 in CRC. Methods The quantitative expressions of CXCL12 and CXCR4 messenger RNA (mRNA) were evaluated in 32 patients with adenocarcinoma-type CRC. Real-time polymerase chain reaction (qRT-PCR) was performed on formalin-fixed tissues. CXCL12 and CXCR4's expressions, clinicopathologic features, and the treatment response to the CRC were analysed. Results All tumour tissues showed higher levels of both chemokines compared to normal colonic tissue. The expression of CXCL12 mRNA was higher in rectal location (p = 0.04) with a tendency to be higher in later stages (p = 0.15), while the expression of CXCR4 was lower in tumours with a lymphatic invasion (p = 0.02), compared to their counterparts. There was no difference in the expression of CXCL12 and CXCR4 according to the patients' ages, gender, tumour differentiation, or response to chemotherapy. Conclusion Our study demonstrated that the mRNA expression of CXCL12 was significantly correlated with rectal location. CXCR4 mRNA expression was inversely correlated in tumours with a lymphatic invasion.

A Pilot Study Investigating the Expression Levels of Pluripotency-Associated Genes in Rectal Swab Samples for Colorectal Polyp and Cancer Diagnosis and Prognosis

“…However, regarding the clinical outcomes, contrary suggestions were raised about whether the level of c-MYC would affect the prognosis and survival of patients [52,53,57]. Uniform results were shown for CXCR4: in agreement with our result, elevated CXCR4 expression was measured in CRC tissues compared with paired normal samples, with the level associated with tumor size, metastasis status, and invasion ability [77,78]. Alternatively, studies of Oct4 and CD26 expression in tissue presented different trends compared with our rectal swab study.…”

Identification of differentially expressed genes and biological characteristics of colorectal cancer by integrated bioinformatics analysis

“…In CRC, CXCL12 (chemokine [C-X-C motif] ligand 12) was mostly reported. It was also considered as hub gene (Liang et al, 2016) and mRNA expression of CXCL12 was significantly correlated with rectal location (Yoshuantari, Heriyanto, Hutajulu, Kurnianda, & Ghozali, 2018). However, there were no significant differences for mRNA CXCL12 between tumor tissues and the adjacent nonaffected tissues (Mousavi et al, 2018).…”

Functional Phenotypes of Peritoneal Macrophages Upon AMD3100 Treatment During Colitis-Associated Tumorigenesis

“…CXCL12 and CXCR4 are independent prognostic factors for tumor differentiation, metastasis, and CRC survival ( 12 , 13 ). Considering the high conservation of the CXCL12/CXCR4 axis across diverse species, studies of CXCR4 inhibitors in mouse and cell lines have the potential to translate into human clinical studies quickly.…”

“…C-X-C motif chemokine ligand 12 (CXCL12) and its receptor C-X-C motif chemokine receptor 4 (CXCR4) have emerged as promising therapeutic approaches targeting tumor growth and metastasis ( 5 ). They were reported to promote cancer progression in several preclinical models, including CRC ( 6 – 11 ), and are independent prognostic factors for tumor differentiation, metastasis, and survival in CRC ( 12 , 13 ). AMD3100 (Plerixafor) is currently the only FDA-approved small molecule CXCR4 antagonist and is the most frequently used drug targeting the CXCL12-CXCR4 axis in clinical trials ( 14 ).…”