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Published in: Tumor Biology 5/2014

01-05-2014 | Research Article

CXCR4 as a novel predictive biomarker for metastasis and poor prognosis in colorectal cancer

Authors: Ying Gao, Chunyu Li, Min Nie, Yao Lu, Shunsen Lin, Peng Yuan, Xun Sun

Published in: Tumor Biology | Issue 5/2014

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Abstract

The clinical significance of CXCR4 expression in colorectal cancer remains unclear. The aim of this study was to investigate the expression and regulatory effects of CXCR4 in colorectal cancer and the association between CXCR4 protein expression and prognosis. The mRNA and protein expression levels of CXCR4 were determined using reverse-transcriptase polymerase chain reaction and immunohistochemistry staining, respectively, and the relationship between the CXCR4 protein level and clinicopathological parameters was analyzed in 720 cases of colorectal cancer. CXCR4 expression was elevated in colorectal cancer tissues compared to pericancerous tissues (P = 0.001). Of the 720 enrolled cases, 208 (28.89 %) expressed CXCR4. In univariate analysis, CXCR4 was found to be associated with lymph node metastasis, TNM stage, and liver metastasis (P = 0.001, 0.001, and 0.012, respectively). Further multivariate analysis suggested that histological grade, TNM stage, and CXCR4 expression were related to liver metastasis (P = 0.020, 0.01, and 0.001, respectively). In the Cox regression test, the histological grade, lymph node metastasis, TNM stage, liver metastasis, and CXCR4 expression were found to be independent prognostic factors (P = 0.02, 0.045, 0.01, 0.001, and 0.001, respectively). CXCR4 protein may be a potential biomarker for liver metastasis and an independent marker for survival in colorectal cancer.
Literature
1.
go back to reference Broadbridge VT, Karapetis CS, Beeke C, Woodman RJ, Padbury R, Maddern G, et al. Do metastatic colorectal cancer patients who present with late relapse after curative surgery have a better survival? Br J Cancer. 2013;109(5):1338–43.CrossRefPubMedPubMedCentral Broadbridge VT, Karapetis CS, Beeke C, Woodman RJ, Padbury R, Maddern G, et al. Do metastatic colorectal cancer patients who present with late relapse after curative surgery have a better survival? Br J Cancer. 2013;109(5):1338–43.CrossRefPubMedPubMedCentral
4.
go back to reference Hyder O, Dodson RM, Mayo SC, Schneider EB, Weiss MJ, Herman JM, et al. Post-treatment surveillance of patients with colorectal cancer with surgically treated liver metastases. Surgery. 2013;154(2):256–65.CrossRefPubMedPubMedCentral Hyder O, Dodson RM, Mayo SC, Schneider EB, Weiss MJ, Herman JM, et al. Post-treatment surveillance of patients with colorectal cancer with surgically treated liver metastases. Surgery. 2013;154(2):256–65.CrossRefPubMedPubMedCentral
5.
go back to reference Eichler K, Dufas T, Hammerstingl R, Gruber-Rouh T, Vogl TJ, Zangos S. Hepatic arterial infusion with irinotecan in patients with liver metastases of colorectal cancer: results of an extended phase I study. Chemotherapy. 2013;59(1):66–73.CrossRefPubMed Eichler K, Dufas T, Hammerstingl R, Gruber-Rouh T, Vogl TJ, Zangos S. Hepatic arterial infusion with irinotecan in patients with liver metastases of colorectal cancer: results of an extended phase I study. Chemotherapy. 2013;59(1):66–73.CrossRefPubMed
6.
go back to reference Bullock MD, Bruce A, Sreekumar R, Curtis N, Cheung T, Reading I, et al. FOXO3 expression during colorectal cancer progression: biomarker potential reflects a tumour suppressor role. Br J Cancer. 2013;109(2):387–94.CrossRefPubMedPubMedCentral Bullock MD, Bruce A, Sreekumar R, Curtis N, Cheung T, Reading I, et al. FOXO3 expression during colorectal cancer progression: biomarker potential reflects a tumour suppressor role. Br J Cancer. 2013;109(2):387–94.CrossRefPubMedPubMedCentral
7.
go back to reference Moriuchi M, Moriuchi H, Turner W, Fauci AS. Cloning and analysis of the promoter region of CXCR4, a coreceptor for HIV-1 entry. J Immunol. 1997;159(9):4322–9.PubMed Moriuchi M, Moriuchi H, Turner W, Fauci AS. Cloning and analysis of the promoter region of CXCR4, a coreceptor for HIV-1 entry. J Immunol. 1997;159(9):4322–9.PubMed
8.
go back to reference Caruz A, Samsom M, Alonso JM, Alcami J, Baleux F, Virelizier JL, et al. Genomic organization and promoter characterization of human CXCR4 gene. FEBS Lett. 1998;426(2):271–8.CrossRefPubMed Caruz A, Samsom M, Alonso JM, Alcami J, Baleux F, Virelizier JL, et al. Genomic organization and promoter characterization of human CXCR4 gene. FEBS Lett. 1998;426(2):271–8.CrossRefPubMed
9.
go back to reference He H, Wang C, Shen Z, Fang Y, Wang X, Chen W, et al. Upregulated expression of C-x-C chemokine receptor 4 is an independent prognostic predictor for patients with gastric cancer. PLoS One. 2013;8(8):e71864.CrossRefPubMedPubMedCentral He H, Wang C, Shen Z, Fang Y, Wang X, Chen W, et al. Upregulated expression of C-x-C chemokine receptor 4 is an independent prognostic predictor for patients with gastric cancer. PLoS One. 2013;8(8):e71864.CrossRefPubMedPubMedCentral
10.
go back to reference Qu QX, Huang Q, Xu J, Duan LT, Zhu YB, Zhang XG. CD40 signal regulates CXCR4 mediating ovarian carcinoma cell migration: implications for extrapelvic metastastic factors. Oncol Res. 2013;20(9):383–92.CrossRefPubMed Qu QX, Huang Q, Xu J, Duan LT, Zhu YB, Zhang XG. CD40 signal regulates CXCR4 mediating ovarian carcinoma cell migration: implications for extrapelvic metastastic factors. Oncol Res. 2013;20(9):383–92.CrossRefPubMed
11.
go back to reference Kremer KN, Peterson KL, Schneider PA, Meng XW, Dai H, Hess AD, et al. CXCR4 chemokine receptor signaling induces apoptosis in acute myeloid leukemia cells via regulation of the Bcl-2 family members Bcl-XL, Noxa, and Bak. J Biol Chem. 2013;288(32):22899–914.CrossRefPubMedPubMedCentral Kremer KN, Peterson KL, Schneider PA, Meng XW, Dai H, Hess AD, et al. CXCR4 chemokine receptor signaling induces apoptosis in acute myeloid leukemia cells via regulation of the Bcl-2 family members Bcl-XL, Noxa, and Bak. J Biol Chem. 2013;288(32):22899–914.CrossRefPubMedPubMedCentral
12.
go back to reference Zhang HW, Sun XF, He YN, Li JT, Guo XH, Liu H. Bioinformatics analysis of breast cancer bone metastasis related gene-CXCR4. Asian Pac J Trop Med. 2013;6(9):732–8.CrossRefPubMed Zhang HW, Sun XF, He YN, Li JT, Guo XH, Liu H. Bioinformatics analysis of breast cancer bone metastasis related gene-CXCR4. Asian Pac J Trop Med. 2013;6(9):732–8.CrossRefPubMed
13.
go back to reference Gillies K, Wertman J, Charette N, Dupré DJ. Anterograde trafficking of CXCR4 and CCR2 receptors in a prostate cancer cell line. Cell Physiol Biochem. 2013;32(1):74–85.CrossRefPubMed Gillies K, Wertman J, Charette N, Dupré DJ. Anterograde trafficking of CXCR4 and CCR2 receptors in a prostate cancer cell line. Cell Physiol Biochem. 2013;32(1):74–85.CrossRefPubMed
14.
go back to reference Strong VE, D'Amico TA, Kleinberg L, Ajani J. Impact of the 7th edition AJCC staging classification on the NCCN clinical practice guidelines in oncology for gastric and esophageal cancers. J Natl Compr Canc Netw. 2013;11(1):60–6.CrossRefPubMed Strong VE, D'Amico TA, Kleinberg L, Ajani J. Impact of the 7th edition AJCC staging classification on the NCCN clinical practice guidelines in oncology for gastric and esophageal cancers. J Natl Compr Canc Netw. 2013;11(1):60–6.CrossRefPubMed
15.
go back to reference Abou-Bakr AA, Elbasmi A. c-MET overexpression as a prognostic biomarker in colorectal adenocarcinoma. Gulf J Oncolog. 2013;1(14):28–34.PubMed Abou-Bakr AA, Elbasmi A. c-MET overexpression as a prognostic biomarker in colorectal adenocarcinoma. Gulf J Oncolog. 2013;1(14):28–34.PubMed
16.
go back to reference Luo DH, Chen QY, Liu H, Xu LH, Zhang HZ, Zhang L, et al. The independent, unfavorable prognostic factors endothelin A receptor and chemokine receptor 4 have a close relationship in promoting the motility of nasopharyngeal carcinoma cells via the activation of AKT and MAPK pathways. J Transl Med. 2013;11(1):203.CrossRefPubMedPubMedCentral Luo DH, Chen QY, Liu H, Xu LH, Zhang HZ, Zhang L, et al. The independent, unfavorable prognostic factors endothelin A receptor and chemokine receptor 4 have a close relationship in promoting the motility of nasopharyngeal carcinoma cells via the activation of AKT and MAPK pathways. J Transl Med. 2013;11(1):203.CrossRefPubMedPubMedCentral
17.
go back to reference Segawa Y, Oda Y, Yamamoto H, Shiratsuchi H, Hirakawa N, Komune S, et al. Close correlation between CXCR4 and VEGF expression and their prognostic implications in nasopharyngeal carcinoma. Oncol Rep. 2009;21(5):1197–202.PubMed Segawa Y, Oda Y, Yamamoto H, Shiratsuchi H, Hirakawa N, Komune S, et al. Close correlation between CXCR4 and VEGF expression and their prognostic implications in nasopharyngeal carcinoma. Oncol Rep. 2009;21(5):1197–202.PubMed
Metadata
Title
CXCR4 as a novel predictive biomarker for metastasis and poor prognosis in colorectal cancer
Authors
Ying Gao
Chunyu Li
Min Nie
Yao Lu
Shunsen Lin
Peng Yuan
Xun Sun
Publication date
01-05-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 5/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1545-x

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