Department of Pathophysiology, Wroclaw Medical University, Wroclaw 50-368, Poland.
Department of Physiotherapy, Wroclaw Medical University, Wroclaw 50-355, Poland.
World J Gastroenterol. 2021 Oct 21;27(39):6673-6688. doi: 10.3748/wjg.v27.i39.6673.
Uncontrolled growth and loss of control over basic metabolic functions, leading to invasive proliferation and metastases, are the salient traits of malignant tumors in general and colorectal cancer in particular. Invasion and metastases hinder effective tumor treatment. While surgical techniques and radiotherapy can be used to remove tumor focus, only chemotherapy can eliminate dispersed neoplastic cells. However, the efficacy of the latter method is limited in the advanced stages of the disease. Therefore, recognition of the mechanisms involved in neoplastic cell spreading is indispensable for developing effective therapies.
To use a number of biomarkers involved in cancer progression and identify a panel that could be used for effective early diagnosis.
We recruited 185 patients with colorectal adenocarcinoma (98 men, 87 women with median age 63). Thirty-five healthy controls were sex and age-matched. Dukes' staging was as follows: A = 22, B = 52, C = 72, D = 39. We analyzed patients' blood serum before surgery. We determined: (1) Cathepsin B (CB) with Barrett's method (fluorogenic substrate); (2) Leukocytic elastase (LE) in a complex with alpha 1 trypsin inhibitor (AAT) using the immunoenzymatic MERCK test; (3) Total sialic acid (TSA) with the colorimetric periodate-resorcinol method; (4) Lipid-bound sialic acid (LASA) with the colorimetric Taut's method; and (5) The antitrypsin activity (ATA) employing the colorimetric test.
In patients, the values of the five biochemical parameters were as follows: CB = 16.1 ± 8.8 mU/L, LE = 875 ± 598 µg/L, TSA = 99 ± 31 mg%, LASA = 0.68 ± 0.33 mg%, and ATA = 3211 ± 1504 U/mL. Except for LASA, they were significantly greater than those of controls: CB = 11.4 ± 6.5 mU/L, LE = 379 ± 187 µg/L, TSA = 71.4 ± 15.1 mg%, LASA = 0.69 ± 0.28 mg%, and ATA = 2016 ± 690 U/mL. For CB and LASA, the differences between the four Dukes' stages and controls were not statistically significant. The inter-stage differences for CB and LASA were also absent. The receiver operating characteristic (ROC) analysis revealed the potential diagnostic value of CB, TSA, and ATA. The area under ROC, sensitivity, and specificity for these three parameters were: 0.85, 72%, 90%; 0.75, 66%, 77%; and 0.77, 63%, 84%, respectively. The sensitivity and specificity for the three-parameter panel CB-TSA-ATA were equal to 88.2% and 100%, respectively.
The increased value of CB, TSA, and ATA parameters are associated with tumor biology, invasion, and metastasis of colorectal cancer. The presented evidence suggests the potential value of the CB-TSA-ATA biochemical marker panel in early diagnostics.
不受控制的生长和对基本代谢功能的失控，导致侵袭性增殖和转移，是恶性肿瘤的显著特征，尤其是结直肠癌。侵袭和转移阻碍了有效的肿瘤治疗。虽然手术技术和放疗可以用于切除肿瘤焦点，但只有化疗才能消除分散的肿瘤细胞。然而，后者的疗效在疾病的晚期受到限制。因此，识别肿瘤细胞扩散涉及的机制对于开发有效的治疗方法是必不可少的。
使用涉及癌症进展的多种生物标志物，并确定可用于有效早期诊断的标志物组合。
我们招募了 185 名患有结直肠腺癌的患者（98 名男性，87 名女性，中位年龄 63 岁）。35 名健康对照者在性别和年龄上相匹配。Dukes 分期如下：A = 22，B = 52，C = 72，D = 39。我们分析了患者手术前的血清。我们测定了：（1）用 Barrett 法（荧光底物）测定组织蛋白酶 B（CB）；（2）用免疫酶 MERCK 试验测定白细胞弹性蛋白酶（LE）与α1 胰蛋白酶抑制剂（AAT）的复合物；（3）用比色过碘酸-间苯二酚法测定总唾液酸（TSA）；（4）用比色 Taut 法测定脂结合唾液酸（LASA）；（5）用比色试验测定抗胰蛋白酶活性（ATA）。
在患者中，五种生化参数的值如下：CB = 16.1 ± 8.8 mU/L，LE = 875 ± 598 µg/L，TSA = 99 ± 31 mg%，LASA = 0.68 ± 0.33 mg%，ATA = 3211 ± 1504 U/mL。除了 LASA，它们都明显高于对照组：CB = 11.4 ± 6.5 mU/L，LE = 379 ± 187 µg/L，TSA = 71.4 ± 15.1 mg%，LASA = 0.69 ± 0.28 mg%，ATA = 2016 ± 690 U/mL。对于 CB 和 LASA，四个 Dukes 分期与对照组之间的差异无统计学意义。CB 和 LASA 的分期间差异也不存在。受试者工作特征（ROC）分析显示了 CB、TSA 和 ATA 的潜在诊断价值。这些三个参数的 ROC 下面积、敏感性和特异性分别为：0.85、72%、90%；0.75、66%、77%；和 0.77、63%、84%。CB-TSA-ATA 三参数组合的敏感性和特异性分别为 88.2%和 100%。
CB、TSA 和 ATA 参数的增加与结直肠癌的肿瘤生物学、侵袭和转移有关。这些证据表明，CB-TSA-ATA 生化标志物组合在早期诊断中有潜在价值。
