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Article type: Research Article
Authors: Amara, Sameha; c; * | Chaar, Inesa; c | Khiari, Meriema; c | Ounissi, Doniaa; c | Weslati, Marwaa; c | Boughriba, Rahmaa; c | Hmida, Abdelmajid B.e | Bouraoui, Saadiaa; b; d
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: [*] 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:he_mas@hotmail.fr
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.
Keywords: Colorectal cancer, chemokineschemokines receptor, liver metastases
DOI: 10.3233/CBM-150531
Journal: Cancer Biomarkers, vol. 15, no. 6, pp. 869-879, 2015
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