肿瘤标志物与结直肠癌术后XELOX辅助化疗疗效的相关性分析

The correlation analysis of tumor markers with the effect of colorectal cancer with XELOX chemotherapy after surgery

目的探讨肿瘤标志物(CEA、VEGF、IGFBP-3、TGF-β1、TIMP-1、miR-21、miR-126、miR-143、miR-148a、miR-192)在结直肠癌XELOX辅助化疗前后的表达变化及与化疗疗效的相关性。方法收集50例健康志愿者,54例结直肠癌患者不同时期(术前、术后化疗前及化疗后)血清样本,运用酶联免疫吸附实验及实时荧光定量PCR法检测样本中上述肿瘤标志物的表达,并分析其与化疗疗效的相关性。结果 XELOX辅助化疗后患者血清中CEA、VEGF、IGFBP-3、TGF-β1、TIMP-1蛋白整体水平显著低于手术前(P<0.05),Ⅱ及Ⅲ期患者化疗后CEA、VEGF、IGFBP-3、TGF-β1、TIMP-1蛋白水平显著低于化疗前(P<0.05),Ⅳ期患者化疗后仅CEA、TGF-β1、TIMP-1水平显著下降(P<0.05);实时荧光定量PCR结果表明:CEA、IGFBP-3、miR-21及miR-126化疗后水平显著低于术前(P<0.05),而与化疗前相比,Ⅱ期患者化疗后CEA、IGFBP-3、miR-21及miR-126显著降低(P<0.05),miR-143显著性增高(P<0.05),Ⅲ期患者化疗后仅CEA、miR-21及miR-126水平显著性降低(P<0.05),其余分子无显著性变化,Ⅳ期患者化疗后与化疗前相比,上述肿瘤标志物分子皆无变化。CEA无论在蛋白水平还是mRNA水平的表达变化与疗效都具有正相关性(mRNA水平Ⅳ期患者除外),IGFBP-3与TGF-β1在蛋白水平的变化与Ⅱ期患者化疗疗效呈正相关,TGF-β1与Ⅲ期患者化疗疗效呈正相关;在mRNA水平,miR-21和miR-126的变化与Ⅱ及Ⅲ期患者化疗疗效呈正相关,其余分子表达变化与疗效无相关性。结论肿瘤标志物的表达变化与结直肠癌不同分期XELOX辅助化疗疗效具有相关性。

Objective To investigate the expression of tumor markers（ CEA,VEGF,IGFBP-3,TGF-β1,TIMP-1,miR-21,miR-126,miR-143,miR-148 a,miR-192） in colorectal cancer with XELOX chemotherapy after surgery,and to detect the correlation between tumor markers and chemotherapy efficacy.Methods Serum samples were collected from 50 healthy volunteers and 54 patients with colorectal cancer at different periods（ preoperative,before and after postoperative chemotherapy）.The expression of tumor markers of colorectal cancer was detected by enzyme-linked immunosorbent assay（ Elisa） and real-time PCR assay,and we analyzedthe relationship between the efficacy of chemotherapy and tumor markers.Results Elisa showed the results that CEA,VEGF,IGFBP-3,TGF-β1,TIMP-1 protein level were significantly lower in patients after XELOX chemotherapy than in preoperative patients（ P〈0.05）,CEA,VEGF,IGFBP-3,TGF-β1,TIMP-1 protein level were significantly lower in patients during stage Ⅱ and Ⅲ after XELOX chemotherapy than in pre-chemotherapy patients（ P〈0.05）,CEA,TGF-β1,TIMP-1 protein level were significantly declined in patients with stage Ⅳaccording to TNM（ P〈0.05）; real-time PCR detected that the mRNA level of CEA,IGFBP-3,miR-21 and miR-126 was lower in patients after XELOX chemotherapy than in preoperative patients（ P〈0.05）,CEA,IGFBP-3,miR-21 and miR-126 mRNA level were significantly lower in patients with stage Ⅱ after XELOX chemotherapy than in pre-chemotherapy patients（ P〈0.05）,and miR-143 was significant higher in patients with stage Ⅱ after XELOX chemotherapy than in pre-chemotherapy patients（ P〈0.05）,CEA、miR-21 and miR-126 were lower in patients with stage Ⅲ after XELOX chemotherapy than in pre-chemotherapy patients（ P〈0.05）,there was no significant change in stage Ⅳ.The expression of CEA at protein and mRNA level have a positive correlation with the chemotherapy efficacy（ except patients in stage Ⅳ）,IGFBP-3 and TGF-β1 protein level have a positive correlation with chemotherapy efficacy in patients with stage Ⅱ,and TGF-β1 protein level have a positive correlation with chemotherapy efficacy in patients with stage Ⅲ; miR-21 and miR-126 have a positive correlation with chemotherapy efficacy in patients with stage Ⅱ and Ⅲ.Conclusions The expression of tumor markers was associated with the effect of XELOX chemotherapy in different stages of colorectal cancer.