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Vasorin is a potential serum biomarker and drug target of hepatocarcinoma screened by subtractive-EMSA-SELEX to clinic patient serum.

Li S, Li H, Yang X, Wang W, Huang A, Li J, Qin X, Li F, Lu G, Ding H, Su X, Hou L, Xia W, Shi M, Zhang H, Zhao Q, Dong J, Ge X, Sun L, Bai C, Wang C, Shen X, Fang T, Wang F, Zhang H, Shao N - Oncotarget (2015)

Bottom Line: VASN was verified to be highly expressed in sera of 100 cases of HCC patients compared with 97 cases of normal persons and 129 cases of hepatitis patients.As a membrane protein and/or as free protein, VASN may be an effective target for biological treatment of liver cancer and is a potential biomarker for HCC diagnosis.Small molecular nucleotides targeting VASN are promising biological therapies to HCC.

View Article: PubMed Central - PubMed

Affiliation: Beijing Institute of Basic Medical Sciences, Beijing, China.

ABSTRACT

Unlabelled: We report a new biomarker of hepatocarcinoma, vasorin (VASN), screened by a subtractive EMSA-SELEX strategy from AFP negative serum of hepatocellular carcinoma (HCC) patients with extrahepatic metastases. VASN was verified to be highly expressed in sera of 100 cases of HCC patients compared with 97 cases of normal persons and 129 cases of hepatitis patients. Further validation by Q-PCR,IFA and Western blot showed higher expression of VASN at mRNA and protein levels in HCC cell lines and HCC tissues than in normal controls. RNA interference and forced overexpression assays verified that VASN promotes cell proliferation and migration and inhibits apoptosis. Down-regulation of microRNA miR145 and miR146a is an important mechanism leading to high expression of VASN.

Conclusion: As a membrane protein and/or as free protein, VASN may be an effective target for biological treatment of liver cancer and is a potential biomarker for HCC diagnosis. Small molecular nucleotides targeting VASN are promising biological therapies to HCC.

No MeSH data available.


Related in: MedlinePlus

VASN is highly expressed in HCC patient serum, tissues and cell lines(a) VASN was verified to be high in HCC sera by a quantitative ELISA assay. The results confirmed the elevation of circulating VASN of HCC patients compared to that of control cohorts. (b) The ROC curve was generated and the area under the curve (AUC) is 0.770. (c) Among the 37 cases of AFP negative serum (37%), 62% of samples were VASN positive (≥ 1.5061ng/ml). (d) VASN mRNA was more highly expressed in hepatocarcinoma tissues than those in hepatocirrhosis, hepatitis and pericarcinoma tissues. (e) VASN mRNA was highly expressed in human hepatoma HepG2, SMMC-7721 cells as measured by real-time PCR. (f) The protein level of VASN was relatively high in human hepatoma HepG2, SMMC-7721 cells measured by Western blot. (g) The expression and localization of VASN protein were verified on HCC tissue slides and benign lesion (hepatitis) liver tissue slides by an indirect immunofluorescence assay. (h) VASN was located on the hepatocellular carcinoma cell surface according to immunofluorescence staining.
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Figure 2: VASN is highly expressed in HCC patient serum, tissues and cell lines(a) VASN was verified to be high in HCC sera by a quantitative ELISA assay. The results confirmed the elevation of circulating VASN of HCC patients compared to that of control cohorts. (b) The ROC curve was generated and the area under the curve (AUC) is 0.770. (c) Among the 37 cases of AFP negative serum (37%), 62% of samples were VASN positive (≥ 1.5061ng/ml). (d) VASN mRNA was more highly expressed in hepatocarcinoma tissues than those in hepatocirrhosis, hepatitis and pericarcinoma tissues. (e) VASN mRNA was highly expressed in human hepatoma HepG2, SMMC-7721 cells as measured by real-time PCR. (f) The protein level of VASN was relatively high in human hepatoma HepG2, SMMC-7721 cells measured by Western blot. (g) The expression and localization of VASN protein were verified on HCC tissue slides and benign lesion (hepatitis) liver tissue slides by an indirect immunofluorescence assay. (h) VASN was located on the hepatocellular carcinoma cell surface according to immunofluorescence staining.

Mentions: We collected sera from 100 proven cases of HCC, 129 cases of hepatitis B and from 97 normal individuals. The VASN level was determined by quantitative ELISA as described in the methods section. The results confirmed the elevation of circulating VASN of HCC patients compared to that of the control cohorts, (Fig. 2a, Supplementary Table 2). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve by SPSS17.0 software was 0.770 (Fig. 2b). The cut-off value was set up as 1.5061ng/ml based on the Youden index so that the sensitivity reached 69% with a specificity of 80.5%. Furthermore, among the 37 cases of AFP negative sera (37%), 23 cases (62%) were VASN positive (≥ 1.5061ng/ml) (Fig. 2c), which suggested that combining the use of AFP and VASN could improve the sensitivity of liver cancer diagnosis. In this report, the diagnostic sensitivity would be increased to 86% from 63% and 69% if combined use of AFP and VASN respectively compared to their use independently.


Vasorin is a potential serum biomarker and drug target of hepatocarcinoma screened by subtractive-EMSA-SELEX to clinic patient serum.

Li S, Li H, Yang X, Wang W, Huang A, Li J, Qin X, Li F, Lu G, Ding H, Su X, Hou L, Xia W, Shi M, Zhang H, Zhao Q, Dong J, Ge X, Sun L, Bai C, Wang C, Shen X, Fang T, Wang F, Zhang H, Shao N - Oncotarget (2015)

VASN is highly expressed in HCC patient serum, tissues and cell lines(a) VASN was verified to be high in HCC sera by a quantitative ELISA assay. The results confirmed the elevation of circulating VASN of HCC patients compared to that of control cohorts. (b) The ROC curve was generated and the area under the curve (AUC) is 0.770. (c) Among the 37 cases of AFP negative serum (37%), 62% of samples were VASN positive (≥ 1.5061ng/ml). (d) VASN mRNA was more highly expressed in hepatocarcinoma tissues than those in hepatocirrhosis, hepatitis and pericarcinoma tissues. (e) VASN mRNA was highly expressed in human hepatoma HepG2, SMMC-7721 cells as measured by real-time PCR. (f) The protein level of VASN was relatively high in human hepatoma HepG2, SMMC-7721 cells measured by Western blot. (g) The expression and localization of VASN protein were verified on HCC tissue slides and benign lesion (hepatitis) liver tissue slides by an indirect immunofluorescence assay. (h) VASN was located on the hepatocellular carcinoma cell surface according to immunofluorescence staining.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4496339&req=5

Figure 2: VASN is highly expressed in HCC patient serum, tissues and cell lines(a) VASN was verified to be high in HCC sera by a quantitative ELISA assay. The results confirmed the elevation of circulating VASN of HCC patients compared to that of control cohorts. (b) The ROC curve was generated and the area under the curve (AUC) is 0.770. (c) Among the 37 cases of AFP negative serum (37%), 62% of samples were VASN positive (≥ 1.5061ng/ml). (d) VASN mRNA was more highly expressed in hepatocarcinoma tissues than those in hepatocirrhosis, hepatitis and pericarcinoma tissues. (e) VASN mRNA was highly expressed in human hepatoma HepG2, SMMC-7721 cells as measured by real-time PCR. (f) The protein level of VASN was relatively high in human hepatoma HepG2, SMMC-7721 cells measured by Western blot. (g) The expression and localization of VASN protein were verified on HCC tissue slides and benign lesion (hepatitis) liver tissue slides by an indirect immunofluorescence assay. (h) VASN was located on the hepatocellular carcinoma cell surface according to immunofluorescence staining.
Mentions: We collected sera from 100 proven cases of HCC, 129 cases of hepatitis B and from 97 normal individuals. The VASN level was determined by quantitative ELISA as described in the methods section. The results confirmed the elevation of circulating VASN of HCC patients compared to that of the control cohorts, (Fig. 2a, Supplementary Table 2). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve by SPSS17.0 software was 0.770 (Fig. 2b). The cut-off value was set up as 1.5061ng/ml based on the Youden index so that the sensitivity reached 69% with a specificity of 80.5%. Furthermore, among the 37 cases of AFP negative sera (37%), 23 cases (62%) were VASN positive (≥ 1.5061ng/ml) (Fig. 2c), which suggested that combining the use of AFP and VASN could improve the sensitivity of liver cancer diagnosis. In this report, the diagnostic sensitivity would be increased to 86% from 63% and 69% if combined use of AFP and VASN respectively compared to their use independently.

Bottom Line: VASN was verified to be highly expressed in sera of 100 cases of HCC patients compared with 97 cases of normal persons and 129 cases of hepatitis patients.As a membrane protein and/or as free protein, VASN may be an effective target for biological treatment of liver cancer and is a potential biomarker for HCC diagnosis.Small molecular nucleotides targeting VASN are promising biological therapies to HCC.

View Article: PubMed Central - PubMed

Affiliation: Beijing Institute of Basic Medical Sciences, Beijing, China.

ABSTRACT

Unlabelled: We report a new biomarker of hepatocarcinoma, vasorin (VASN), screened by a subtractive EMSA-SELEX strategy from AFP negative serum of hepatocellular carcinoma (HCC) patients with extrahepatic metastases. VASN was verified to be highly expressed in sera of 100 cases of HCC patients compared with 97 cases of normal persons and 129 cases of hepatitis patients. Further validation by Q-PCR,IFA and Western blot showed higher expression of VASN at mRNA and protein levels in HCC cell lines and HCC tissues than in normal controls. RNA interference and forced overexpression assays verified that VASN promotes cell proliferation and migration and inhibits apoptosis. Down-regulation of microRNA miR145 and miR146a is an important mechanism leading to high expression of VASN.

Conclusion: As a membrane protein and/or as free protein, VASN may be an effective target for biological treatment of liver cancer and is a potential biomarker for HCC diagnosis. Small molecular nucleotides targeting VASN are promising biological therapies to HCC.

No MeSH data available.


Related in: MedlinePlus