Affiliations: [a] Laboratory of Colorectal Cancer Research UR03ES04, Science University Tunis, Tunis, Tunisia | [b] Department of Pathology and Cytology, Mongi Slim Hospital, La Marsa, Tunis, Tunisia | [c] Faculty of Sciences UTM, University Tunis El Manar, Tunis, Tunisia | [d] Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia | [e] Department of Epidemiology and Preventive Medicine, Medicine University Tunis, Tunis, Tunisia
Correspondence:
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Corresponding author: Sameh Amara, Laboratory of Colorectal Cancer Research UR12SP14, Department of Pathology and Cytology, Mongi Slim Hospital, 2047 SidiDaoud, Tunis, Tunisia. Tel.: +216 2139 7876; Fax: +216 5419 7876; E-mail:[email protected]
Abstract: BACKGROUND: Recent studies suggest that SDF-1 and CXCR4 are expressed in
certain cancer cells, and malignant cells use this chemokine/receptor system
to promote tumor progression and metastasis. However, the pathophysiological
significance of their expression in colorectal cancer (CRC) tissue has not
been fully elucidated.
OBJECTIVE: The purpose of this study was to assess SDF-1/CXCR4 expression
and to explore its contribution to colorectal cancer.
METHODS: We examined SDF-1 and CXCR4 mRNA expression in 124 primary
colorectal tumour and 35 liver metastases tissues and matched adjacent
noncancerous tissues by reverse transcriptase PCR (RT-PCR). Furthermore,
their expression was analyzed by immunohistochemistry. The relationship
between SDF-1/CXCR4 expression and clinicopathological features were
analyzed by appropriate statistics. X2 test and Kaplan-Meier analysis were
used to investigate the correlation between the ligand-receptor expression
and prognosis of colorectal cancer patients.
RESULTS: The relative mRNA expression of SDF-1 and CXCR4 was significantly
elevated in colorectal cancer tissues as compared with adjacent noncancerous
tissues (P < 0.001). The high expression of proteins expression in
colorectal cancer tissues was significantly correlated with tumor grade
(P = 0.0001), clinical stage (P < 0.05), and lymphatic invasion (P < 0.05).
Furthermore, patients with CXCR4 nuclear-type expression showed more
frequent lymph node metastasis (p = 0.021), advanced clinical stage
(p = 0.001) and lymphatic invasion (p = 0.03) than those with cytoplasm
staining-type. Kaplan-Meier survival analysis revealed that high expression
of the couple SDF-1/CXCR4 correlated with poor prognosis of colorectal
cancer patients (P < 0.001).
CONCLUSION: SDF-1 and CXCR4 may play an important role in the progression of
colorectal cancer. The present data suggest that there is a significant
association between SDF-1/CXCR4 to enhance the liver metastases causing poor
prognosis. Those proteins may potentially be used as an independent
biomarker for the prognostic evaluation of colon cancer in the Tunisian
cohort.
