Abstract：
OBJECTIVE: Classical serum cancer biomarkers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), remain important tools in colorectal cancer (CRC) management for disease follow up. However, their sensitivity and specificity are low for diagnostic and prognostic evaluation. The aim of this study was to evaluate the potential of biomarkers reflecting biological activity of tumors - tissue polypeptide specific antigen (TPS), cytokeratin fragment 19 (CYFRA 21-1), thymidine kinase (TK), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGF-BP3) - together with the CEA and CA 19-9 in CRC diagnosis and prognosis.
METHODS: This is a retrospective study including 148 CRC patients and 68 age-matched healthy subjects. Serum biomarkers were measured in pre-operative serum samples using immunoanalytical methods. The end-point for the diagnostic evaluation was the area under the receiving operating characteristic curve (AUC ROC) of the biomarkers. The end-point for the prognostic evaluation was overall survival.
RESULTS: Serum levels of CEA, CA 19-9, TPS, and TK were significantly increased in CRC early-stage patients compared with healthy controls. Each of the studied biomarkers had AUC between 0.6 and 0.7. Analysis of survival demonstrated that the patients with CEA, CA 19-9, cytokeratin, and TK above optimal cut offs had significantly shorter survival. A multivariate analysis performed on all the study biomarkers resulted in the selection of CYFRA 21-1 as the best performing biomarker with hazard ratio 10.413.
CONCLUSIONS: The combination of cytokeratins and thymidine kinase with classical cancer biomarkers enables the prediction of tumor aggressiveness and long-term prognosis.
METHODS: This is a retrospective study including 148 CRC patients and 68 age-matched healthy subjects. Serum biomarkers were measured in pre-operative serum samples using immunoanalytical methods. The end-point for the diagnostic evaluation was the area under the receiving operating characteristic curve (AUC ROC) of the biomarkers. The end-point for the prognostic evaluation was overall survival.
RESULTS: Serum levels of CEA, CA 19-9, TPS, and TK were significantly increased in CRC early-stage patients compared with healthy controls. Each of the studied biomarkers had AUC between 0.6 and 0.7. Analysis of survival demonstrated that the patients with CEA, CA 19-9, cytokeratin, and TK above optimal cut offs had significantly shorter survival. A multivariate analysis performed on all the study biomarkers resulted in the selection of CYFRA 21-1 as the best performing biomarker with hazard ratio 10.413.
CONCLUSIONS: The combination of cytokeratins and thymidine kinase with classical cancer biomarkers enables the prediction of tumor aggressiveness and long-term prognosis.
摘要：
目标：经典血清癌症生物标志物，如癌胚抗原（CEA）和癌症抗原19-9（CA19-9），仍然是结直肠癌（CRC）疾病随访管理的重要工具。然而,其诊断和预后评估的敏感性和特异性较低.这项研究的目的是评估反映肿瘤生物活性的生物标志物的潜力-组织多肽特异性抗原（TPS），细胞角蛋白片段19（CYFRA21-1），胸苷激酶(TK),胰岛素样生长因子1（IGF-1）和胰岛素样生长因子结合蛋白3（IGF-BP3）-与CEA和CA19-9一起用于CRC诊断和预后。
方法：这是一项回顾性研究，包括148例CRC患者和68例年龄匹配的健康受试者。使用免疫分析方法测量术前血清样品中的血清生物标志物。诊断评估的终点是生物标志物的接收操作特征曲线(AUC/ROC)下的面积。预后评估的终点是总生存期。
结果：血清CEA水平，CA19-9,TPS,与健康对照组相比,早期CRC患者的TK显著升高.每个研究的生物标志物的AUC在0.6和0.7之间。生存分析表明，CEA患者，CA19-9，细胞角蛋白，TK高于最佳截止值的生存期明显缩短。对所有研究生物标志物进行的多变量分析导致选择CYFRA21-1作为表现最好的生物标志物,风险比10.413。
结论：细胞角蛋白和胸苷激酶与经典癌症生物标志物的组合能够预测肿瘤侵袭性和长期预后。
方法：这是一项回顾性研究，包括148例CRC患者和68例年龄匹配的健康受试者。使用免疫分析方法测量术前血清样品中的血清生物标志物。诊断评估的终点是生物标志物的接收操作特征曲线(AUC/ROC)下的面积。预后评估的终点是总生存期。
结果：血清CEA水平，CA19-9,TPS,与健康对照组相比,早期CRC患者的TK显著升高.每个研究的生物标志物的AUC在0.6和0.7之间。生存分析表明，CEA患者，CA19-9，细胞角蛋白，TK高于最佳截止值的生存期明显缩短。对所有研究生物标志物进行的多变量分析导致选择CYFRA21-1作为表现最好的生物标志物,风险比10.413。
结论：细胞角蛋白和胸苷激酶与经典癌症生物标志物的组合能够预测肿瘤侵袭性和长期预后。
