4th Department-Internal Medicine, 4th Medical Discipline, Faculty of Medicine, "Iuliu Haţieganu" University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania.
6th Department-Surgery, 4th Surgery Discipline, Faculty of Medicine, "Iuliu Haţieganu" University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania.
Int J Mol Sci. 2024 May 3;25(9):4997. doi: 10.3390/ijms25094997.
Colorectal cancer (CRC) is one of the most common neoplasms in developed countries, with increasing incidence and mortality, even in young people. A variety of serum markers have been associated with CRC (CEA, CA 19-9), but neither should be used as a screening tool for the diagnosis or evolution staging of CRC. The sensitivity and specificity of these markers are not as good as is required, so new ones need to be found. Matrix Gla protein and PIVKA II are involved in carcinogenesis, but few studies have evaluated their usefulness in predicting the presence and severity of CRC. Two hundred patients were divided into three groups: 80 patients were included in the control group; 80 with CRC and without hepatic metastasis were included in Group 1; 40 patients with CRC and hepatic metastasis were included in Group 2. Vitamin K-dependent proteins (VKDPs) levels in plasma were determined. Patients with CRC without methastasis (Group 1) and CRC patients with methastasis (Group 2) presented significantly higher values of CEA, CA 19-9, PIVKA II (310.05 ± 38.22 vs. 430.13 ± 122.13 vs. 20.23 ± 10.90), and ucMGP (14,300.00 ± 2387.02 vs. 13,410.52 ± 2243.16 vs. 1780.31 ± 864.70) compared to control group (Group 0). Interestingly, Group 1 presented the greatest PIVKA II values. Out of all the markers, significant differences between the histological subgroups were found only for ucMGP, but only in non-metastatic CRC. Studying the discrimination capacity between the patients with CRC vs. those without, no significant differences were found between the classical tumor markers and the VKDP AUROC curves (PIVKA II and ucMGP AUROCs = 1). For the metastatic stage, the sensitivity and specificity of the VKDPs were lower in comparison with those of CA 19-9 and CEA, respectively (PIVKA II AUROC = 0.789, ucMGP AUROC = 0.608). The serum levels of these VKDPs are significantly altered in patients with colorectal carcinoma; it is possible to find additional value of these in the early stages of the disease.
结直肠癌（CRC）是发达国家最常见的肿瘤之一，其发病率和死亡率呈上升趋势，甚至在年轻人中也是如此。有多种血清标志物与 CRC 相关（CEA、CA 19-9），但都不应作为 CRC 诊断或分期的筛查工具。这些标志物的敏感性和特异性都不如预期，因此需要寻找新的标志物。基质 Gla 蛋白和 PIVKA II 参与了癌变，但很少有研究评估它们在预测 CRC 存在和严重程度方面的有用性。将 200 名患者分为三组：80 名患者纳入对照组；80 名无肝转移的 CRC 患者纳入第 1 组；40 名有肝转移的 CRC 患者纳入第 2 组。检测血浆中维生素 K 依赖蛋白（VKDPs）水平。无转移的 CRC 患者（第 1 组）和有转移的 CRC 患者（第 2 组）的 CEA、CA 19-9、PIVKA II（310.05±38.22 比 430.13±122.13 比 20.23±10.90）和 ucMGP（14,300.00±2387.02 比 13,410.52±2243.16 比 1780.31±864.70）值显著升高，与对照组（第 0 组）相比。有趣的是，第 1 组的 PIVKA II 值最高。在所有标志物中，仅在非转移性 CRC 患者中发现 ucMGP 在组织学亚组之间存在显著差异。在研究 CRC 患者与无 CRC 患者之间的鉴别能力时，经典肿瘤标志物与 VKDPs 的 AUROC 曲线（PIVKA II 和 ucMGP AUROCs=1）之间无显著差异。对于转移阶段，与 CA 19-9 和 CEA 相比，VKDPs 的敏感性和特异性较低（PIVKA II AUROC=0.789，ucMGP AUROC=0.608）。这些 VKDPs 的血清水平在结直肠癌患者中显著改变，因此有可能在疾病的早期阶段发现这些标志物的额外价值。
