RAGE、sRAGE在结肠癌中的表达及其临床意义

Clinical significance of abnormal tissue RAGE and serum sRAGE expression in colorectal cancer

目的:本研究通过检测结肠癌组织晚期糖基化终末产物受体(the receptor for advanced glycation end product,RAGE)和血清可溶性RAGE(soluble RAGE,sRAGE)的表达水平,探讨其在结肠癌发生、发展过程中的作用及其临床意义。方法:本研究纳入49例非糖尿病结肠癌(I、II、III期)患者,以免疫组织化学评分法(immunohistochemical score,IHS)评价结肠癌RAGE表达水平,以ELISA法检测患者外周血血清sRAGE浓度。结果:结肠癌组织RAGE表达水平(IHS为1.24±0.48)显著高于癌周组织(IHS为0.50±0.25)(P<0.05),III期(IHS为1.42±0.51)显著性高于I期(IHS为1.01±0.35)(P<0.05)和II期(IHS为1.11±0.42)(P<0.05);低分化结肠癌组织(IHS为1.58±0.49)显著高于中分化(IHS为1.08±0.45)(P<0.05)和高分化结肠癌组织(IHS为1.02±0.27)(P<0.05)。结肠癌患者血清sRAGE表达水平术前、术后分别为(344.77±68.06)ng/L、(265.43±76.85)ng/L,二者相比有显著性差异(P<0.05),而且分别与健康志愿者sRAGE(149.97±30.12)ng/L相比有显著性差异(P<0.05),但sRAGE表达水平与TNM分期、结肠癌组织分化程度没有关联。结肠癌组织RAGE高表达患者术前血清sRAGE浓度(415.02±85.08)ng/L高于中表达(334.26±44.56)ng/L和低表达(335.95±78.48)ng/L患者(P<0.05)。结论:结肠癌组织RAGE表达水平与分化程度呈负相关趋势,与TNM分期呈正相关趋势,作为术后诊断指标有一定的临床意义。血清sRAGE浓度与结肠癌组织RAGE表达水平呈正相关趋势,但与TNM分期和结肠癌组织分化程度没有关联,作为术前诊断指标仅能代表结肠癌风险,但无法考量结肠癌的恶性程度和进展情况。

Objective： To investigate the correlation and the clinical significance of the expression of the receptor of advanced glycation end product（ RAGE） and the soluble RAGE（ sRAGE） in colorectal cancer tissue. Methods：To study the expression of RAGE on colorectal carcinoma cells,pathological paraffin blocks of 49 colorectal cancer patients without diabetes mellitus were enrolled in this study,and 10 adjacent tissues（ cancer tissue edge ≥5cm） as control group. The expression of RAGE was analyzed by immunehistochemical staining. To detect the concentration of serum sRAGE,peripheral blood of 49 colorectal cancer patients were collected at about 24 hours before operation and7 th day after surgery. And the peripheral bloods of 30 healthy donors were collected as control group. The serum of blood samples were separated,and the concentrations of serum sRAGE were analyzed by ELISA. Results： The expression of colorectal cancer tissue RAGE（ IHS： 1. 24 ± 0. 48） was significantly higher than that of control group（ IHS：0. 50 ± 0. 25）（ P〈0. 05）,and the stage Ⅲ was significantly higher than stageⅠ（ 1. 01 ± 0. 35）（ P〈0. 05） and Ⅱ（ 1. 11 ± 0. 42）（ P〈0. 05）. The RAGE expression of poorly differentiated colorectal cancer tissue（ IHS： 1. 58 ±0. 49） was significantly higher than that of moderately differentiated tissues（ IHS： 1. 08 ± 0. 45） and well- differentiated tissues（ IHS： 1. 02 ± 0. 27）（ P〈0. 05）. The concentration of serum sRAGE after radical colorectal cancer resection（ 265. 43 ± 76. 85） was below preoperative level（ 344. 77 ± 68. 06）（ P〈0. 05）,and both of them were higher than that of healthy donors（ 149. 97 ± 30. 12）（ P〈0. 05）,but was no associated with TNM and pathological differentiation. The preoperative serum sRAGE concentration of higher RAGE expression patients（ 415. 02 ± 85. 08） ng /L is higher than that of moderate level RAGE expression patients（ 334. 26 ± 44. 56） ng / L and lower level RAGE expression patients（ 335. 95 ± 78. 48） ng / L（ P〈0. 05）. Conclusion： RAGE expression was negatively related to colorectal cancer differentiation,and positively correlated trends with TNM. Serum sRAGE concentration was positively correlated with colorectal cancer tissue RAGE expression,but no associated with TNM and pathological differentiation.RAGE examination for the diagnosis of colorectal cancer after surgery has clinical significance,but the serum sRAGE examination before surgery for colorectal cancer diagnosis can only show a colorectal cancer risk.