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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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IHC for DC-SIGN and DC-SIGNR expression in colon cancer tissues and in matched normal colonic mucosa of colon cancer patients.Areas in the black boxes of A, C, E, G, IandA, C, E, G, I were enlarged below. A-B: DC-SIGN expression was detected in the internal border, central and peripheral part of colon carcinoma. C–D: blank control primary human colon cancer sections (without anti-DC-SIGN pAb). E–F: DC-SIGN expression in matched normal colonic mucosa. G–H: DC-SIGN expression was mainly detected in human lymphoid sinus. I–J: blank control human lymph node sections (without anti-DC-SIGN pAb); A–B: DC-SIGNR expression was weakly detected in the invasive margin of tumor. C–D: blank control primary human colon cancer sections. E–F: DC-SIGN expression was negative in matched normal colonic mucosa, while the G and H were positive controls in the human lymph node. I–J: blank control human lymph node sections. Magnification:100× in A, C, E,A, C, E, G,I; 200× in G, I; 400× in B, D, F, H, J, B, D, F, H, J.
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pone-0114748-g004: IHC for DC-SIGN and DC-SIGNR expression in colon cancer tissues and in matched normal colonic mucosa of colon cancer patients.Areas in the black boxes of A, C, E, G, IandA, C, E, G, I were enlarged below. A-B: DC-SIGN expression was detected in the internal border, central and peripheral part of colon carcinoma. C–D: blank control primary human colon cancer sections (without anti-DC-SIGN pAb). E–F: DC-SIGN expression in matched normal colonic mucosa. G–H: DC-SIGN expression was mainly detected in human lymphoid sinus. I–J: blank control human lymph node sections (without anti-DC-SIGN pAb); A–B: DC-SIGNR expression was weakly detected in the invasive margin of tumor. C–D: blank control primary human colon cancer sections. E–F: DC-SIGN expression was negative in matched normal colonic mucosa, while the G and H were positive controls in the human lymph node. I–J: blank control human lymph node sections. Magnification:100× in A, C, E,A, C, E, G,I; 200× in G, I; 400× in B, D, F, H, J, B, D, F, H, J.

Mentions: We determined the expression level of both DC-SIGN and DC-SIGNR in serum. Moreover, it has been reported that immature DC-SIGN+ dendritic cells are present within primary colorectal cancer tissues [14], [26]. Our team previously found that DC-SIGNR is expressed in both cancer tissues and serum of NHL patients [23]. We therefore speculated that DC-SIGN and DC-SIGNR may be expressed in colon cancer tissues. IHC for DC-SIGN and DC-SIGNR was performed using 98 colon cancer tissues for DC-SIGN and 20 cancer tissues for DC-SIGNR, with the staining intensity determined by a pathologist who was blinded to the relevant clinical information. DC-SIGN staining in matched normal colonic mucosa was faint (Fig. 4E and 4F), while intense DC-SIGN staining was observed in the tumor stroma and the invasive margins of colon cancer tissues (Fig. 4A and 4B). The negative controls are shown in Fig. 4C and 4D. DC-SIGN staining in the lymph nodes, used as a positive control, are shown in Fig. 4G and 4H.


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)

IHC for DC-SIGN and DC-SIGNR expression in colon cancer tissues and in matched normal colonic mucosa of colon cancer patients.Areas in the black boxes of A, C, E, G, IandA, C, E, G, I were enlarged below. A-B: DC-SIGN expression was detected in the internal border, central and peripheral part of colon carcinoma. C–D: blank control primary human colon cancer sections (without anti-DC-SIGN pAb). E–F: DC-SIGN expression in matched normal colonic mucosa. G–H: DC-SIGN expression was mainly detected in human lymphoid sinus. I–J: blank control human lymph node sections (without anti-DC-SIGN pAb); A–B: DC-SIGNR expression was weakly detected in the invasive margin of tumor. C–D: blank control primary human colon cancer sections. E–F: DC-SIGN expression was negative in matched normal colonic mucosa, while the G and H were positive controls in the human lymph node. I–J: blank control human lymph node sections. Magnification:100× in A, C, E,A, C, E, G,I; 200× in G, I; 400× in B, D, F, H, J, B, D, F, H, J.
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pone-0114748-g004: IHC for DC-SIGN and DC-SIGNR expression in colon cancer tissues and in matched normal colonic mucosa of colon cancer patients.Areas in the black boxes of A, C, E, G, IandA, C, E, G, I were enlarged below. A-B: DC-SIGN expression was detected in the internal border, central and peripheral part of colon carcinoma. C–D: blank control primary human colon cancer sections (without anti-DC-SIGN pAb). E–F: DC-SIGN expression in matched normal colonic mucosa. G–H: DC-SIGN expression was mainly detected in human lymphoid sinus. I–J: blank control human lymph node sections (without anti-DC-SIGN pAb); A–B: DC-SIGNR expression was weakly detected in the invasive margin of tumor. C–D: blank control primary human colon cancer sections. E–F: DC-SIGN expression was negative in matched normal colonic mucosa, while the G and H were positive controls in the human lymph node. I–J: blank control human lymph node sections. Magnification:100× in A, C, E,A, C, E, G,I; 200× in G, I; 400× in B, D, F, H, J, B, D, F, H, J.
Mentions: We determined the expression level of both DC-SIGN and DC-SIGNR in serum. Moreover, it has been reported that immature DC-SIGN+ dendritic cells are present within primary colorectal cancer tissues [14], [26]. Our team previously found that DC-SIGNR is expressed in both cancer tissues and serum of NHL patients [23]. We therefore speculated that DC-SIGN and DC-SIGNR may be expressed in colon cancer tissues. IHC for DC-SIGN and DC-SIGNR was performed using 98 colon cancer tissues for DC-SIGN and 20 cancer tissues for DC-SIGNR, with the staining intensity determined by a pathologist who was blinded to the relevant clinical information. DC-SIGN staining in matched normal colonic mucosa was faint (Fig. 4E and 4F), while intense DC-SIGN staining was observed in the tumor stroma and the invasive margins of colon cancer tissues (Fig. 4A and 4B). The negative controls are shown in Fig. 4C and 4D. DC-SIGN staining in the lymph nodes, used as a positive control, are shown in Fig. 4G and 4H.

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