Co-expression of CXCR4 and CD133 proteins is associated with poor prognosis in stage II–III colon cancer patients

Zhang, Nianhua; Li, Jie; Li, Yin; Zhang, Xintao; Liao, Wenting; Zhang, Jun‐Yi; Li, Rong; Luo, Rong

doi:10.3892/etm.2012.527

Cited by 27 publications

(18 citation statements)

References 54 publications

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“…Hematological malignancy (7 studies, 764 patients) [12-18], breast cancer (18 studies, 4125 patients) [10, 11, 19-34], colorectal cancer (7 studies, 515 patients) [35-41], esophageal cancer (7 studies, 886 patients) [42-48], gastric cancer (5 studies, 755 patients) [49-53], head and neck cancer (7 studies, 577 patients) [54-60], renal cancer (6 studies, 764 patients) [61-66], lung cancer (7 studies, 727 patients) [8, 67-72], melanoma (4 studies, 168 patients) [73-76], gynecologic cancer (8 studies, 826 patients) [9, 77-83], pancreatic cancer (2 studies, 320 patients) [84, 85], prostate cancer (2 studies, 109 patients) [86, 87], liver cancer (2 studies, 256 patients) [88, 89], sarcoma (2 studies, 168 patients) [90, 91] and gallbladder cancer (1 study, 72 patients) [92] were evaluated in current meta-analysis as shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…The pooled model showed a significantly shorter OS with CXCR4 over-expression patients in hematological malignancy (7 studies, 764 patients, HR=1.93, 95% CI, 1.33-2.79, Figure 10) [12-18], breast cancer (18 studies, 4125 patients, HR=1.58, 95% CI, 1.29-1.94, Figure 11) [10, 11, 19-34], colorectal cancer (5 studies, 375 patients, HR=1.83, 95% CI, 1.32-2.53, Figure 12) [36, 37, 39-41], esophageal cancer (7 studies, 886 patients, HR=1.65, 95% CI, 1.24-2.19, Figure 13) [42-48], head and neck cancer (7 studies, 577 patients, HR=2.02, 95% CI, 1.37-2.97, Figure 14) [54-60], renal cancer (5 studies, 594 patients, HR=2.93, 95% CI, 2.06-4.15, Figure 15) [61, 62, 64-66], lung cancer (6 studies, 573 patients, HR=2.51, 95% CI, 1.64-3.83, Figure 16) [8, 67-69, 71, 72], gynecologic cancer (7 studies, 796 patients, HR=2.24, 95% CI, 1.11-4.50, Figure 17) [9, 77-82], liver cancer (2 studies, 256 patients, HR=2.75, 95% CI, 2.02-3.75) [88, 89], prostate cancer (2 studies, 109 patients, HR=2.67, 95% CI, 1.61-4.42) [86, 87] and gallbladder cancer (1 studies, 72 patients, HR=2.30, 95% CI, 1.10-4.80) [92]. Based on the available data, the associations between CXCR4 over-expression and PFS were inconclusive in gastric cancer (5 studies, 755 patients, HR=1.94, 95% CI, 0.86-4.35, Figure 18) [49-53], melanoma (3 studies, 136 patients, HR=1.93, 95% CI, 0.88-4.25, Figure 19) [74-76], pancreatic cancer (2 studies, 320 patients, HR=1.34, 95% CI, 0.63-2.83) [84, 85] and sarcoma (2 studies, 168 patients, HR=5.14, 95% CI, 0.64-41.50) [90, 91].…”

Section: Resultsmentioning

confidence: 99%

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CXCR4 over-expression and survival in cancer: A system review and meta-analysis

et al. 2014

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C-X-C chemokine receptor 4 (CXCR4) is frequently over-expressed in various types of cancer; many agents against CXCR4 are in clinical development currently despite variable data for the prognostic impact of CXCR4 expression. Here eighty-five studies with a total of 11,032 subjects were included to explore the association between CXCR4 and progression-free survival (PFS) or overall survival (OS) in subjects with cancer. Pooled analysis shows that CXCR4 over-expression is significantly associated with poorer PFS (HR 2.04; 95% CI, 1.72-2.42) and OS (HR=1.94; 95% CI, 1.71-2.20) irrespective of cancer types. Subgroup analysis indicates significant association between CXCR4 and shorter PFS in hematological malignancy, breast cancer, colorectal cancer, esophageal cancer, renal cancer, gynecologic cancer, pancreatic cancer and liver cancer; the prognostic effects remained consistent across age, risk of bias, levels of adjustment, median follow-up period, geographical area, detection methods, publication year and size of studies. CXCR4 over-expression predicts unfavorable OS in hematological malignancy, breast cancer, colorectal cancer, esophageal cancer, head and neck cancer, renal cancer, lung cancer, gynecologic cancer, liver cancer, prostate cancer and gallbladder cancer; these effects were independence of age, levels of adjustment, publication year, detection methods and follow-up period. In conclusion, CXCR4 over-expression is associated with poor prognosis in cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

CXCR4 over-expression and survival in cancer: A system review and meta-analysis

et al. 2014

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“…In Zhang’s study, 125 stage II or III colon cancer specimens without neoadjuvant chemoradiotherapy were obtained after radical resection. 90 patients received postoperative Fu-based adjuvant chemotherapy and 35 stage II patients did not receive adjuvant interventions[48]. Li’s study included 200 colorectal adenocarcinomas and adjuvant chemoradiotherapy was not provided[49].…”

Section: Resultsmentioning

confidence: 99%

CD133 Expression and the Prognosis of Colorectal Cancer: A Systematic Review and Meta-Analysis

et al. 2013

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ObjectiveCD133 has recently been reported as a marker of cancer stem-like cells in colorectal cancer (CRC). However, its predictive value in CRC still remains controversial. In this study, we aimed to evaluate the association between the expression of CD133 and clinicopathological features and the outcome of CRC patients by performing a meta-analysis.MethodsA comprehensive literature search for relevant studies published up to December 2012 was performed using PubMed, MEDLINE and ISI Web of Science. Only articles in which CD133 antigen was detected in situ localisation by immunohistochemical staining were included. This meta-analysis was done using RevMan 4.2 software.ResultsWe found that a total of 15 studies involving 810 CD133-high and 1487 CD133-low patients met the inclusion criteria for the analysis of 5-year overall survival (OS) rate. In a random-effects model, the results showed that CD133-high expression in colorectal cancer was an independent prognostic marker correlating with both OS rate (RR = 0.67, 95%CI 0.54–0.82, P<0.01) and disease free survival (DFS) rate (RR = 0.71, 95%CI 0.52–0.96, P = 0.03). CD133-high expression was also associated with more T3,4 tumor invasion, N positive and vascular invasion cases, corresponding to a risk difference of 1.12 (95%CI 1.01–1.23, P = 0.03), 1.31 (95%CI 1.06–1.63, P = 0.01) and 1.24 (95%CI 1.08–1.41, P<0.01), respectively. However, when types of histology, lymphatic invasion and distant metastasis were considered, CD133 overexpression was not significantly related with these clinicopathological parameters.ConclusionOur meta-analysis results suggest that CD133 is an efficient prognostic factor in CRC. Higher CD133 expression is significantly associated with poorer clinical outcome and some clinicopathological factors such as T category, N category and vascular invasion in CRC patients.

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“…CXCR4 has been considered as a potential therapeutic target in several studies. A number of in vitro studies have reported that inhibiting the interactions of chemokine CXCR4 using antibodies or small molecules markedly reduces the metastasis of colorectal cancer cells (30,31); this approach could become a promising therapy for colon cancer.…”

Section: Discussionmentioning

confidence: 99%

Expression of CXCR-4 and IDO in human colorectal cancer: An immunohistochemical approach

Ogawa

Watanabe

Hasegawa

et al. 2017

Molecular and Clinical Oncology

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Abstract. C-X-C chemokine receptor type 4 (CXCR4), the receptor for the chemokine stromal cell-derived factor (SDF)-1 [also known as C-X-C motif chemokine 12 (CXCL12)], is involved in lymphocyte trafficking. Recent studies have demonstrated that, during pregnancy, a placental enzyme called indoleamine 2, 3-dioxygenase (IDO) exerts a key role in suppressing the maternal T-cell response against the fetus. In the present study, the significance of CXCR4 and IDO expression in human colorectal cancer (CRC) has been investigated by immunohistochemical assay, and their association with survival was analyzed. Tumor specimens (n=60) from patients with different American Joint Committee on Cancer (AJCC) stages of CRC (I or IV) were assessed. In the stage IV group, 23 of 30 cases (77%) stained positive for CXCR4, and 9 of 30 (30%) were positive for IDO. By contrast, in the stage I group, 7 of 30 cases (23%) stained positive for CXCR4, and 15 of 30 cases (50%) were positive for IDO. The 5-year survival rate of those with high CXCR4 expression in tumor specimens (n=30) was significantly worse compared with those with negative CXCR4 expression (16.3 vs. 60.7%, P=0.02). By contrast, the 5-year survival rate of those with high IDO expression in tumor specimens (n=24) was not significantly different compared with those with negative IDO expression (36.4 vs. 56.8%). In the stage I group, 4 patients in the high IDO expression group (n=15) had distant metastases (2 in the liver 1 in the brain, and 1 in the lung). Taken together, CXCR4 appears to be a novel predictive indicator of survival, and IDO expression in the early stage may be a predictor of distant metastasis.

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Co-expression of CXCR4 and CD133 proteins is associated with poor prognosis in stage II–III colon cancer patients

Cited by 27 publications

References 54 publications

CXCR4 over-expression and survival in cancer: A system review and meta-analysis

CXCR4 over-expression and survival in cancer: A system review and meta-analysis

CD133 Expression and the Prognosis of Colorectal Cancer: A Systematic Review and Meta-Analysis

Expression of CXCR-4 and IDO in human colorectal cancer: An immunohistochemical approach

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