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      Relationship and prognostic significance of SPARC and VEGF protein expression in colon cancer

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          Abstract

          Background

          SPARC (secreted protein, acidic and rich in cysteine) is closely related with the progress, invasion and metastasis of malignant tumor and angiogenesis.

          Methods

          Using human colon adenocarcinoma tissues (hereinafter referred to as colon cancer) and their corresponding non-diseased colon from 114 patients' biopsies, the expression of SPARC and vascular endothelial growth factor (VEGF) were investigated by immunohistochemistry staining to assessment the relationship between SPARC and VEGF, as well as their prognostic significance in patients. Evaluation of VEGF expression level with the same tissues was used to establish the antigenic profiles, and the marker of CD34 staining was used as an indicator of microvessel density (MVD).

          Results

          SPARC expression was mainly in the stromal cells surrounding the colon cancer, and was significant difference in those tissues with the lymph node metastasis and differentiation degree of tumor. Expression of SPARC was significantly correlated with the expression of VEGF and MVD in colon cancer tissues. Patients with low or absence expressing SPARC had significantly worse overall survival and disease-free survival in a Single Factor Analysis; Cox Regression Analysis, SPARC emerged as an overall survival and disease-free survival independent prognostic factor for colon cancer.

          Conclusion

          The low expression or absence of stromal SPARC was an independent prognostic factor for poor prognosis of colon cancer. SPARC maybe involved in the regulation of anti-angiogenesis by which it may serve as a novel target for colon cancer treatment as well as a novel distinctive marker.

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          Most cited references33

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          SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury.

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            Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature

            We performed a meta-analysis of all published studies relating intratumoural microvessel density (MVD) (45 studies) or vascular endothelial growth factor (VEGF) expression (27 studies), both reflecting angiogenesis, to relapse free (RFS) and overall survival (OS) in colorectal cancer (CRC). For each study, MVD impact was measured by risk ratio between the two survival distributions with median MVD as cutoff. Eleven studies did not mention survival data or fit inclusion criteria, six were multiple publications of same series, leaving 32 independent studies for MVD (3496 patients) and 18 for VEGF (2050 patients). Microvessel density was assessed by immunohistochemistry, using antibodies against factor VIII (16 studies), CD31 (10 studies) or CD34 (seven studies). Vascular endothelial growth factor expression was mostly assessed by immunohistochemistry. Statistics were performed for MVD in 22 studies (the others lacking survival statistics) including nine studies (n=957) for RFS and 18 for OS (n=2383) and for VEGF in 17 studies, including nine studies for RFS (n=1064) and 10 for OS (n=1301). High MVD significantly predicted poor RFS (RR=2.32 95% CI: 1.39–3.90; P<0.001) and OS (RR=1.44; 95% CI: 1.08–1.92; P=0.01). Using CD31 or CD34, MVD was inversely related to survival, whereas it was not using factor VIII. Vascular endothelial growth factor expression significantly predicted poor RFS (RR=2.84; 95% CI: 1.95–4.16) and OS (RR=1.65; 95% CI: 1.27–2.14). To strengthen our findings, future prospective studies should explore the relation between MVD or VEGF expression and survival or response to therapy (e.g. antiangiogenic therapy). Assessment of these angiogenic markers should be better standardised in future studies.
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              SPARC in cancer biology: its role in cancer progression and potential for therapy.

              The ability to effectively target a tumor to achieve complete regression and cure is the ultimate goal that drives our need to better understand tumor biology. Recently, SPARC has generated considerable interest as a multi-faceted protein that belongs to a family of matricellular proteins. It functions not only to modulate cell-cell and cell-matrix interactions, but its de-adhesive and growth inhibitory properties in non-transformed cells have led to studies to assess its role in cancer. Its divergent actions reflect the complexity of this protein, because in certain types of cancers, such as melanomas and gliomas, SPARC is associated with a highly aggressive tumor phenotype, while in others, mainly ovarian, neuroblastomas and colorectal cancers, SPARC may function as a tumor suppressor. Recent studies have also demonstrated a role for SPARC in sensitizing therapy-resistant cancers. Here, the role of SPARC in cancer progression and its potential application in cancer therapy is discussed.
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                Author and article information

                Journal
                J Exp Clin Cancer Res
                Journal of Experimental & Clinical Cancer Research : CR
                BioMed Central
                0392-9078
                1756-9966
                2010
                16 June 2010
                : 29
                : 1
                : 71
                Affiliations
                [1 ]Dept of Pathology, First Clinical Medical College, Shanxi Medical University, Taiyuan City, Shanxi, China
                [2 ]Dept of Pediatrics, Shanxi Medical University, Taiyuan City, Shanxi, China
                [3 ]Dept of Surgery, First Clinical Medical College, Shanxi Medical University, Taiyuan
                Article
                1756-9966-29-71
                10.1186/1756-9966-29-71
                2895582
                20565704
                4f4b9c07-01db-40fa-914f-b717066768b8
                Copyright ©2010 Liang et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 January 2010
                : 16 June 2010
                Categories
                Research

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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