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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

Kaplan-Meier analysis of SPON2 expression in CRC patients based on the Oncomine dataset mining and TMA-IHC analysisA. Overall survival analysis of CRC patients with different SPON2 gene expression using Smith Colorectal 2 dataset from Oncomine database. The low or high expression of SPON2 was defined as lower-than the median or higher-than the median. B. Disease-free survival analysis of CRC patients with different SPON2 expression using Smith Colorectal 2 dataset. C. Positive SPON2 protein expression in CRC patients predicted poor prognosis as revealed by TMA-IHC analysis. The commercial TMA contains 90 CRC cases, while those cases without follow-up information and/or without detectable epithelial cells were excluded from the analysis. The p value was calculated using the Log-rank (Mantel-Cox) test.
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Figure 3: Kaplan-Meier analysis of SPON2 expression in CRC patients based on the Oncomine dataset mining and TMA-IHC analysisA. Overall survival analysis of CRC patients with different SPON2 gene expression using Smith Colorectal 2 dataset from Oncomine database. The low or high expression of SPON2 was defined as lower-than the median or higher-than the median. B. Disease-free survival analysis of CRC patients with different SPON2 expression using Smith Colorectal 2 dataset. C. Positive SPON2 protein expression in CRC patients predicted poor prognosis as revealed by TMA-IHC analysis. The commercial TMA contains 90 CRC cases, while those cases without follow-up information and/or without detectable epithelial cells were excluded from the analysis. The p value was calculated using the Log-rank (Mantel-Cox) test.

Mentions: To address the protein change of SPON2 in colon cancer tissues, we performed IHC analyses of SPON2 expression using two commercial independent TMAs, each of which contains 90 cases of colorectal adenocarcinoma. The stained TMAs were scanned and images of each cases were extracted and subjected to the analysis of mean integrated optical density (IOD) using Image Pro Plus. Only the IOD of cancer epithelial cells in each images were analyzed and the values from different area and different images of the same sample were averaged. Some samples were excluded from analysis due to the absence of visible epithelial cancer cells. The expression of SPON2 protein was substantially upregulated in CRC tissues (n = 173) comparing with the normal counterparts (n = 166) (unpaired Student's t test, p = 3.5E-6) (Figure 2B). The difference was more significant by comparing 159 paired normal and cancer samples (paired, two-sided Student's t test, p value = 8.1E-7). The staining of negative and positive SPON2 expression in the normal colonic mucosa tissues were shown in Figure 2C and 2D, respectively. The negative staining of SPON2 of one CRC tissue sample was depicted in Figure 3E. In addition, the typical weak and strong SPON2 staining of CRC tissues were displayed in Figure 3F and 3G, respectively.


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)

Kaplan-Meier analysis of SPON2 expression in CRC patients based on the Oncomine dataset mining and TMA-IHC analysisA. Overall survival analysis of CRC patients with different SPON2 gene expression using Smith Colorectal 2 dataset from Oncomine database. The low or high expression of SPON2 was defined as lower-than the median or higher-than the median. B. Disease-free survival analysis of CRC patients with different SPON2 expression using Smith Colorectal 2 dataset. C. Positive SPON2 protein expression in CRC patients predicted poor prognosis as revealed by TMA-IHC analysis. The commercial TMA contains 90 CRC cases, while those cases without follow-up information and/or without detectable epithelial cells were excluded from the analysis. The p value was calculated using the Log-rank (Mantel-Cox) test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Kaplan-Meier analysis of SPON2 expression in CRC patients based on the Oncomine dataset mining and TMA-IHC analysisA. Overall survival analysis of CRC patients with different SPON2 gene expression using Smith Colorectal 2 dataset from Oncomine database. The low or high expression of SPON2 was defined as lower-than the median or higher-than the median. B. Disease-free survival analysis of CRC patients with different SPON2 expression using Smith Colorectal 2 dataset. C. Positive SPON2 protein expression in CRC patients predicted poor prognosis as revealed by TMA-IHC analysis. The commercial TMA contains 90 CRC cases, while those cases without follow-up information and/or without detectable epithelial cells were excluded from the analysis. The p value was calculated using the Log-rank (Mantel-Cox) test.
Mentions: To address the protein change of SPON2 in colon cancer tissues, we performed IHC analyses of SPON2 expression using two commercial independent TMAs, each of which contains 90 cases of colorectal adenocarcinoma. The stained TMAs were scanned and images of each cases were extracted and subjected to the analysis of mean integrated optical density (IOD) using Image Pro Plus. Only the IOD of cancer epithelial cells in each images were analyzed and the values from different area and different images of the same sample were averaged. Some samples were excluded from analysis due to the absence of visible epithelial cancer cells. The expression of SPON2 protein was substantially upregulated in CRC tissues (n = 173) comparing with the normal counterparts (n = 166) (unpaired Student's t test, p = 3.5E-6) (Figure 2B). The difference was more significant by comparing 159 paired normal and cancer samples (paired, two-sided Student's t test, p value = 8.1E-7). The staining of negative and positive SPON2 expression in the normal colonic mucosa tissues were shown in Figure 2C and 2D, respectively. The negative staining of SPON2 of one CRC tissue sample was depicted in Figure 3E. In addition, the typical weak and strong SPON2 staining of CRC tissues were displayed in Figure 3F and 3G, respectively.

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