Chemokine receptor CXCR4 expression is correlated with VEGF expression and poor survival in soft‐tissue sarcoma

Abstract

The expression of chemokine receptor CXCR4 has been associated with poor prognosis and VEGF expression in several kinds of human malignancy. We measured CXCR4 expression levels in soft‐tissue sarcoma and compared them with VEGF expression or microvessel density (MVD). We used real‐time quantitative PCR to examine the CXCR4 and VEGF expression levels in a total 176 tumors, including 24 intermediate tumors, 24 malignant round‐cell tumors (MRCTs) and 128 malignant non‐round‐cell tumors (MNRCTs). We also assessed their immunohistochemical expression of CXCR4 and VEGF, MVD and proliferative activities, as measured by the MIB‐1‐labeling index (LI). Furthermore, we evaluated their significance with respect to patient survival rates in MNRCTs, using the Cox regression model. Within the different types of tumor tissue, the expression levels of CXCR4 (p < 0.0001) and VEGF (p < 0.0001) in MNRCTs were significantly higher than those in intermediate tumors or MRCTs. Immunohistochemical expression levels of CXCR4 and VEGF were significantly correlated with their mRNA expression levels (p < 0.0001). Significant positive correlation was found between CXCR4 and VEGF expression in 112 primary MNRCTs (r = 0.434, p < 0.0001). Moreover, both univariate (p < 0.0001) and Cox multivariate analysis (p = 0.0001) revealed that overexpression of CXCR4 was an independent adverse prognostic factor, in addition to high stage according to the American Joint Committee on Cancer and a high MIB‐1‐LI. Determination of the CXCR4 expression level as a novel marker can provide useful prognostic information for patients and it could be a candidate for molecular targeting therapy in MNRCTs of soft‐tissue sarcomas. © 2008 Wiley‐Liss, Inc.

Local Mesenchymal Stem/Progenitor Cells Are a Preferential Target for Initiation of Adult Soft Tissue Sarcomas Associated with p53 and Rb Deficiency

“…It has been previously reported that signaling through CXCR4 plays an important role in progression of a broad variety of malignancies, including breast cancers, 37 prostate cancers, 38 malignant melanomas, 37,39 gastric cancer, 40 osteosarcomas, 41 and rhabdomyosarcomas. 42 In agreement with a previous report that expression of CXCR4 is associated with poor prognosis of STS 34 we observed that expression of CXCR4 is significantly higher in high-grade sarcomas, such as UPS and leiomyosarcomas as compared to low-grade dermatofibrosarcoma and fibrosarcoma. Furthermore, according to our Matrigel invasion assays, stimulation of Cxcr4 by addition of Sdf-1 increased invasion of sarcoma cells, while siRNA-mediated knockdown of Cxcr4 significantly reduced their invasion.…”

“…It has been reported that the expression of CXCR4 in human STSs is associated with poor prognosis and metastasis, 34 particularly in malignant nonround cell tumors such as UPS and leiomyosarcoma. In agreement with these observations, we determined high expression of CXCR4 in human UPS (MFH) and leiomyosarcoma (Table 2).…”

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

“…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.…”

“…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]. The insignificant associations between these subtypes of cancer and clinical outcome might be due to the limited available data.…”

Prognostic significance of Minichromosome maintenance protein 7 and Geminin expression in patients with 109 soft tissue sarcomas

“…It is necessary to select the appropriate therapy for patients with STSs due to their different pathobiological behavior and prognostic significance. A number of prognostic or biological markers were studied in STSs and reported to be significant prognostic markers (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”