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Upregulation of spondin-2 predicts poor survival of colorectal carcinoma patients.

Zhang Q, Wang XQ, Wang J, Cui SJ, Lou XM, Yan B, Qiao J, Jiang YH, Zhang LJ, Yang PY, Liu F - Oncotarget (2015)

Bottom Line: Here we found that Spondin-2 mRNA was upregulated in CRC tissues using quantitative RT-PCR and data-mining of public Oncomine microarray datasets.Spondin-2 gene expression was significantly associated with CRC stage, T stage, M stage and Dukes stage, while its protein was associated with age and M stage.Receiver operating characteristic curve analysis demonstrated that plasma Spondin-2 has superior predictive performance for CRC with an area under the curve of 0.959 and the best sensitivity/specificity of 100%/90%.

View Article: PubMed Central - PubMed

Affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

ABSTRACT
Colorectal cancer (CRC) is the third and second most common cancer in males and females worldwide, respectively. Spondin-2 is a conserved secreted extracellular matrix protein and a candidate cancer biomarker. Here we found that Spondin-2 mRNA was upregulated in CRC tissues using quantitative RT-PCR and data-mining of public Oncomine microarray datasets. Spondin-2 protein was increased in CRC tissues, as revealed by immunohistochemistry analyses of two tissue microarrays containing 180 cases. Spondin-2 gene expression was significantly associated with CRC stage, T stage, M stage and Dukes stage, while its protein was associated with age and M stage. Kaplan-Meier analysis revealed that the upregulated Spondin-2 mRNA and protein predicted poor prognosis of CRC patients. Univariate and multivariate Cox regression analyses indicated that grade, recurrence, N stage and high Spondin-2 were independent predictors of overall survival of CRC patients. ELISA revealed that plasma Spondin-2 was upregulated in CRC and dropped after surgery. Receiver operating characteristic curve analysis demonstrated that plasma Spondin-2 has superior predictive performance for CRC with an area under the curve of 0.959 and the best sensitivity/specificity of 100%/90%. Furthermore, ectopic expression of Spondin-2 enhanced colon cancer cell proliferation. Spondin-2 could be an independent diagnostic and prognostic biomarker of colon cancer.

No MeSH data available.


Related in: MedlinePlus

The functional role of SPON2 in colon cancer cell linesA. SPON2 protein levels in colon cancer cell lines were analyzed using Western blot. B.SPON2 was overexpressed in colon cell lines HCT-116 and SW-620 and the expression level of SPON2 was analyzed using Western blot. C. Growth curve analysis of SPON2 ectopic expression in colon cancer cells was performed using the MTT method. The p values were calculated using replicated data by Student's t test and p < 0.05 was considered as statistically significant. D. The SPON2 was overexpressed in SW-620 cell and the migration was measured using Transwell method. The cells migrated to the bottom of the membrane were stained with crystal violet and the dye was dissolved using acetic acid and absorbance was measured at 570 nm.
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Figure 5: The functional role of SPON2 in colon cancer cell linesA. SPON2 protein levels in colon cancer cell lines were analyzed using Western blot. B.SPON2 was overexpressed in colon cell lines HCT-116 and SW-620 and the expression level of SPON2 was analyzed using Western blot. C. Growth curve analysis of SPON2 ectopic expression in colon cancer cells was performed using the MTT method. The p values were calculated using replicated data by Student's t test and p < 0.05 was considered as statistically significant. D. The SPON2 was overexpressed in SW-620 cell and the migration was measured using Transwell method. The cells migrated to the bottom of the membrane were stained with crystal violet and the dye was dissolved using acetic acid and absorbance was measured at 570 nm.

Mentions: To get further insight into the functional role of SPON2 in tumorigenesis of colon cancer, we performed in vitro proliferation assays using colon cancer cell lines. Western blot analysis of SPON2 expression indicated that SPON2 was abundant in colon cancer cell lines HT-29, LoVo and Caco-2, but low in HCT-116, SW-480 and SW-620 (Figure 5A). We then overexpressed the full-length SPON2 gene in HCT-116 and SW-620 (Figure 5B). The proliferation of both cells were measured using methylthiazolyldiphenyl-tetrazolium bromide (MTT)assay, which revealed that the upregulated SPON2 induced an significantly accelerated proliferation of HCT-116 and SW-620 (Figure 5C). We also analysed the migration potential of SW-620 cells with ectopic expressed SPON2. However, no significant change was observed after SPON2 expression (Figure 5D).


Upregulation of spondin-2 predicts poor survival of colorectal carcinoma patients.

Zhang Q, Wang XQ, Wang J, Cui SJ, Lou XM, Yan B, Qiao J, Jiang YH, Zhang LJ, Yang PY, Liu F - Oncotarget (2015)

The functional role of SPON2 in colon cancer cell linesA. SPON2 protein levels in colon cancer cell lines were analyzed using Western blot. B.SPON2 was overexpressed in colon cell lines HCT-116 and SW-620 and the expression level of SPON2 was analyzed using Western blot. C. Growth curve analysis of SPON2 ectopic expression in colon cancer cells was performed using the MTT method. The p values were calculated using replicated data by Student's t test and p < 0.05 was considered as statistically significant. D. The SPON2 was overexpressed in SW-620 cell and the migration was measured using Transwell method. The cells migrated to the bottom of the membrane were stained with crystal violet and the dye was dissolved using acetic acid and absorbance was measured at 570 nm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4558138&req=5

Figure 5: The functional role of SPON2 in colon cancer cell linesA. SPON2 protein levels in colon cancer cell lines were analyzed using Western blot. B.SPON2 was overexpressed in colon cell lines HCT-116 and SW-620 and the expression level of SPON2 was analyzed using Western blot. C. Growth curve analysis of SPON2 ectopic expression in colon cancer cells was performed using the MTT method. The p values were calculated using replicated data by Student's t test and p < 0.05 was considered as statistically significant. D. The SPON2 was overexpressed in SW-620 cell and the migration was measured using Transwell method. The cells migrated to the bottom of the membrane were stained with crystal violet and the dye was dissolved using acetic acid and absorbance was measured at 570 nm.
Mentions: To get further insight into the functional role of SPON2 in tumorigenesis of colon cancer, we performed in vitro proliferation assays using colon cancer cell lines. Western blot analysis of SPON2 expression indicated that SPON2 was abundant in colon cancer cell lines HT-29, LoVo and Caco-2, but low in HCT-116, SW-480 and SW-620 (Figure 5A). We then overexpressed the full-length SPON2 gene in HCT-116 and SW-620 (Figure 5B). The proliferation of both cells were measured using methylthiazolyldiphenyl-tetrazolium bromide (MTT)assay, which revealed that the upregulated SPON2 induced an significantly accelerated proliferation of HCT-116 and SW-620 (Figure 5C). We also analysed the migration potential of SW-620 cells with ectopic expressed SPON2. However, no significant change was observed after SPON2 expression (Figure 5D).

Bottom Line: Here we found that Spondin-2 mRNA was upregulated in CRC tissues using quantitative RT-PCR and data-mining of public Oncomine microarray datasets.Spondin-2 gene expression was significantly associated with CRC stage, T stage, M stage and Dukes stage, while its protein was associated with age and M stage.Receiver operating characteristic curve analysis demonstrated that plasma Spondin-2 has superior predictive performance for CRC with an area under the curve of 0.959 and the best sensitivity/specificity of 100%/90%.

View Article: PubMed Central - PubMed

Affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

ABSTRACT
Colorectal cancer (CRC) is the third and second most common cancer in males and females worldwide, respectively. Spondin-2 is a conserved secreted extracellular matrix protein and a candidate cancer biomarker. Here we found that Spondin-2 mRNA was upregulated in CRC tissues using quantitative RT-PCR and data-mining of public Oncomine microarray datasets. Spondin-2 protein was increased in CRC tissues, as revealed by immunohistochemistry analyses of two tissue microarrays containing 180 cases. Spondin-2 gene expression was significantly associated with CRC stage, T stage, M stage and Dukes stage, while its protein was associated with age and M stage. Kaplan-Meier analysis revealed that the upregulated Spondin-2 mRNA and protein predicted poor prognosis of CRC patients. Univariate and multivariate Cox regression analyses indicated that grade, recurrence, N stage and high Spondin-2 were independent predictors of overall survival of CRC patients. ELISA revealed that plasma Spondin-2 was upregulated in CRC and dropped after surgery. Receiver operating characteristic curve analysis demonstrated that plasma Spondin-2 has superior predictive performance for CRC with an area under the curve of 0.959 and the best sensitivity/specificity of 100%/90%. Furthermore, ectopic expression of Spondin-2 enhanced colon cancer cell proliferation. Spondin-2 could be an independent diagnostic and prognostic biomarker of colon cancer.

No MeSH data available.


Related in: MedlinePlus