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The clinical significance of DC-SIGN and DC-SIGNR, which are novel markers expressed in human colon cancer.

Jiang Y, Zhang C, Chen K, Chen Z, Sun Z, Zhang Z, Ding D, Ren S, Zuo Y - PLoS ONE (2014)

Bottom Line: Furthermore, there were significant differences between both sDC-SIGN and sDC-SIGNR in stage I/II patients and the healthy controls.Interestingly, the percent survival of patients with a DC-SIGN mean density of>0.001219 (the upper 95% confidence interval of matched normal colon tissues) was higher than for all other patients.DC-SIGN and DC-SIGNR are blood-based molecular markers that can potentially be used for the diagnosis of early stage patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China; Department of Clinical Laboratory, the First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.

ABSTRACT

Background: Colon cancer has always been diagnosed at a late stage, which is associated with poor prognosis. The currently used serum tumor markers CEA and CA19-9 display low sensitivity and specificity and may not have diagnostic value in early stage colon cancer. Thus, there is an urgent need to identify novel serum biomarkers for use in the early detection of colon cancer.

Methods: In this study, the expression of DC-SIGN and DC-SIGNR in serum was detected by enzyme-linked immunosorbent assay (ELISA). DC-SIGN and DC-SIGNR expression was detected in cancer tissues by immunohistochemistry (IHC).

Results: The level of sDC-SIGN was lower in patients than in the healthy controls, while the level of sDC-SIGNR in patients was higher than in the healthy controls. Both sDC-SIGN and sDC-SIGNR had diagnostic significances for cancer patients, and the combined diagnosis of these two markers was higher than both of them alone. Furthermore, there were significant differences between both sDC-SIGN and sDC-SIGNR in stage I/II patients and the healthy controls. Moreover, high sDC-SIGN level was accompanied with the long survival time. Additionally, DC-SIGNR was negative in the cancer foci and matched normal colon tissues but was weakly positive between the cancer foci. DC-SIGN staining was faint in matched normal colon tissues, strong in the tumor stroma and the invasive margin of colon cancer tissues, and negatively correlated with the sDC-SIGN level in serum from the same patient. Interestingly, the percent survival of patients with a DC-SIGN mean density of>0.001219 (the upper 95% confidence interval of matched normal colon tissues) was higher than for all other patients.

Conclusion: DC-SIGN and DC-SIGNR are blood-based molecular markers that can potentially be used for the diagnosis of early stage patients. Moreover, expression of DC-SIGN in serum and cancer tissues may affect the survival time for colon cancer patients.

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Related in: MedlinePlus

The early diagnostic values of sDC-SIGN and sDC-SIGNR in stage I/II colon cancer patients.A–B: Both sDC-SIGN and sDC-SIGNR levels from early colon cancer patients. Stage I/II patients were significantly different from healthy people, P<0.01. sDC-SIGN is lower than in the healthy control, while sDC-SIGNR is higher. C–D: In the stage I/II patients, sDC-SIGN and sDC-SIGNR had a significant diagnostic value (P<0.01). The cut-off concentrations of DC-SIGN and DC-SIGNR were less than 2.211 µg/ml and more than 189.3 ng/ml, respectively. The corresponding sensitivity and specificity of the two molecules were 81.33% and 55.56%, 48.65% and 92.50%, respectively. E–F: The AUC of CEA and CA19-9 in early cancer were 0.6904 and 0.6917. At the above clinical decisive level, the sensitivity of both CEA (18.64) and CA19-9 (10.00) were very low, while, the specificity of both CEA (92.33) and CA19-9 (94.55) was high. G: The comparison between the ROC curves of four markers, DC-SIGN, DC-SIGNR, CEA and CA19-9. There were significant differences between the AUCs of sDC-SIGN and both sDC-SIGNR and CA19-9. According to the cut-off values for sDC-SIGN and sDC-SIGNR obtained from the ROC curves, CEA and CA19-9 from the clinical decisive level, the sensitivity (diagnostic values) of both sDC-SIGN (81%) and sDC-SIGNR (49%) were higher than CEA (19%) and CA19-9 (10%).
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pone-0114748-g002: The early diagnostic values of sDC-SIGN and sDC-SIGNR in stage I/II colon cancer patients.A–B: Both sDC-SIGN and sDC-SIGNR levels from early colon cancer patients. Stage I/II patients were significantly different from healthy people, P<0.01. sDC-SIGN is lower than in the healthy control, while sDC-SIGNR is higher. C–D: In the stage I/II patients, sDC-SIGN and sDC-SIGNR had a significant diagnostic value (P<0.01). The cut-off concentrations of DC-SIGN and DC-SIGNR were less than 2.211 µg/ml and more than 189.3 ng/ml, respectively. The corresponding sensitivity and specificity of the two molecules were 81.33% and 55.56%, 48.65% and 92.50%, respectively. E–F: The AUC of CEA and CA19-9 in early cancer were 0.6904 and 0.6917. At the above clinical decisive level, the sensitivity of both CEA (18.64) and CA19-9 (10.00) were very low, while, the specificity of both CEA (92.33) and CA19-9 (94.55) was high. G: The comparison between the ROC curves of four markers, DC-SIGN, DC-SIGNR, CEA and CA19-9. There were significant differences between the AUCs of sDC-SIGN and both sDC-SIGNR and CA19-9. According to the cut-off values for sDC-SIGN and sDC-SIGNR obtained from the ROC curves, CEA and CA19-9 from the clinical decisive level, the sensitivity (diagnostic values) of both sDC-SIGN (81%) and sDC-SIGNR (49%) were higher than CEA (19%) and CA19-9 (10%).

Mentions: According to a recent report, regenerating islet-derived protein 4 (REG4), a member of the C-type lectin superfamily, may be a good serum marker for the early diagnosis of gastric cancer [25]. We therefore analyzed the diagnostic values of sDC-SIGN and sDC-SIGNR in stage I/II colon cancer. Importantly, we found that the levels of sDC-SIGN and sDC-SIGNR in stage I/II cancer patients were 1.452±0.867 µg/ml and 505.5±645.1 ng/ml, respectively. These levels were significantly different than those in the healthy controls, P<0.05 (Fig. 2A–2B). In contrast to the higher level of sDC-SIGNR in early stage colon cancer patients relative to healthy controls, the level of sDC-SIGN in colon cancer was lower than in cancer-free people.


The clinical significance of DC-SIGN and DC-SIGNR, which are novel markers expressed in human colon cancer.

Jiang Y, Zhang C, Chen K, Chen Z, Sun Z, Zhang Z, Ding D, Ren S, Zuo Y - PLoS ONE (2014)

The early diagnostic values of sDC-SIGN and sDC-SIGNR in stage I/II colon cancer patients.A–B: Both sDC-SIGN and sDC-SIGNR levels from early colon cancer patients. Stage I/II patients were significantly different from healthy people, P<0.01. sDC-SIGN is lower than in the healthy control, while sDC-SIGNR is higher. C–D: In the stage I/II patients, sDC-SIGN and sDC-SIGNR had a significant diagnostic value (P<0.01). The cut-off concentrations of DC-SIGN and DC-SIGNR were less than 2.211 µg/ml and more than 189.3 ng/ml, respectively. The corresponding sensitivity and specificity of the two molecules were 81.33% and 55.56%, 48.65% and 92.50%, respectively. E–F: The AUC of CEA and CA19-9 in early cancer were 0.6904 and 0.6917. At the above clinical decisive level, the sensitivity of both CEA (18.64) and CA19-9 (10.00) were very low, while, the specificity of both CEA (92.33) and CA19-9 (94.55) was high. G: The comparison between the ROC curves of four markers, DC-SIGN, DC-SIGNR, CEA and CA19-9. There were significant differences between the AUCs of sDC-SIGN and both sDC-SIGNR and CA19-9. According to the cut-off values for sDC-SIGN and sDC-SIGNR obtained from the ROC curves, CEA and CA19-9 from the clinical decisive level, the sensitivity (diagnostic values) of both sDC-SIGN (81%) and sDC-SIGNR (49%) were higher than CEA (19%) and CA19-9 (10%).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4264775&req=5

pone-0114748-g002: The early diagnostic values of sDC-SIGN and sDC-SIGNR in stage I/II colon cancer patients.A–B: Both sDC-SIGN and sDC-SIGNR levels from early colon cancer patients. Stage I/II patients were significantly different from healthy people, P<0.01. sDC-SIGN is lower than in the healthy control, while sDC-SIGNR is higher. C–D: In the stage I/II patients, sDC-SIGN and sDC-SIGNR had a significant diagnostic value (P<0.01). The cut-off concentrations of DC-SIGN and DC-SIGNR were less than 2.211 µg/ml and more than 189.3 ng/ml, respectively. The corresponding sensitivity and specificity of the two molecules were 81.33% and 55.56%, 48.65% and 92.50%, respectively. E–F: The AUC of CEA and CA19-9 in early cancer were 0.6904 and 0.6917. At the above clinical decisive level, the sensitivity of both CEA (18.64) and CA19-9 (10.00) were very low, while, the specificity of both CEA (92.33) and CA19-9 (94.55) was high. G: The comparison between the ROC curves of four markers, DC-SIGN, DC-SIGNR, CEA and CA19-9. There were significant differences between the AUCs of sDC-SIGN and both sDC-SIGNR and CA19-9. According to the cut-off values for sDC-SIGN and sDC-SIGNR obtained from the ROC curves, CEA and CA19-9 from the clinical decisive level, the sensitivity (diagnostic values) of both sDC-SIGN (81%) and sDC-SIGNR (49%) were higher than CEA (19%) and CA19-9 (10%).
Mentions: According to a recent report, regenerating islet-derived protein 4 (REG4), a member of the C-type lectin superfamily, may be a good serum marker for the early diagnosis of gastric cancer [25]. We therefore analyzed the diagnostic values of sDC-SIGN and sDC-SIGNR in stage I/II colon cancer. Importantly, we found that the levels of sDC-SIGN and sDC-SIGNR in stage I/II cancer patients were 1.452±0.867 µg/ml and 505.5±645.1 ng/ml, respectively. These levels were significantly different than those in the healthy controls, P<0.05 (Fig. 2A–2B). In contrast to the higher level of sDC-SIGNR in early stage colon cancer patients relative to healthy controls, the level of sDC-SIGN in colon cancer was lower than in cancer-free people.

Bottom Line: Furthermore, there were significant differences between both sDC-SIGN and sDC-SIGNR in stage I/II patients and the healthy controls.Interestingly, the percent survival of patients with a DC-SIGN mean density of>0.001219 (the upper 95% confidence interval of matched normal colon tissues) was higher than for all other patients.DC-SIGN and DC-SIGNR are blood-based molecular markers that can potentially be used for the diagnosis of early stage patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China; Department of Clinical Laboratory, the First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.

ABSTRACT

Background: Colon cancer has always been diagnosed at a late stage, which is associated with poor prognosis. The currently used serum tumor markers CEA and CA19-9 display low sensitivity and specificity and may not have diagnostic value in early stage colon cancer. Thus, there is an urgent need to identify novel serum biomarkers for use in the early detection of colon cancer.

Methods: In this study, the expression of DC-SIGN and DC-SIGNR in serum was detected by enzyme-linked immunosorbent assay (ELISA). DC-SIGN and DC-SIGNR expression was detected in cancer tissues by immunohistochemistry (IHC).

Results: The level of sDC-SIGN was lower in patients than in the healthy controls, while the level of sDC-SIGNR in patients was higher than in the healthy controls. Both sDC-SIGN and sDC-SIGNR had diagnostic significances for cancer patients, and the combined diagnosis of these two markers was higher than both of them alone. Furthermore, there were significant differences between both sDC-SIGN and sDC-SIGNR in stage I/II patients and the healthy controls. Moreover, high sDC-SIGN level was accompanied with the long survival time. Additionally, DC-SIGNR was negative in the cancer foci and matched normal colon tissues but was weakly positive between the cancer foci. DC-SIGN staining was faint in matched normal colon tissues, strong in the tumor stroma and the invasive margin of colon cancer tissues, and negatively correlated with the sDC-SIGN level in serum from the same patient. Interestingly, the percent survival of patients with a DC-SIGN mean density of>0.001219 (the upper 95% confidence interval of matched normal colon tissues) was higher than for all other patients.

Conclusion: DC-SIGN and DC-SIGNR are blood-based molecular markers that can potentially be used for the diagnosis of early stage patients. Moreover, expression of DC-SIGN in serum and cancer tissues may affect the survival time for colon cancer patients.

Show MeSH
Related in: MedlinePlus