División de Medicina Molecular, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS)..
Servicio de Oncología Médica, Centro Médico Nacional de Occidente (CMNO) Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México.
Cell Mol Biol (Noisy-le-grand). 2022 Jun 30;68(6):1-8. doi: 10.14715/cmb/2022.68.6.1.
Colorectal cancer (CRC) is the third most common cancer in the world. Overall survival is related to clinical stage: more advanced stages show lower survival rates; therefore, they need to be monitored regularly with new, less invasive and more specific biomarkers. The concentration and integrity index of circulating cell-free DNA (ccfDNA) have been proposed as potential diagnostic and prognostic biomarkers for CRC, however, inconsistent results are still observed in different reports. Here we analyze these potential CRC biomarkers in a Mexican population. In this study, 124 patients with sporadic CRC and 37 healthy individuals were examined as a reference group. The ccfDNA was isolated from plasma samples of all included subjects. The ccfDNA concentration was determined by fluorometry and the integrity index (ALU247/ALU115 ratio) by quantitative PCR amplification (qPCR) of ALU sequences. The results show that ccfDNA concentration was higher in CRC patients than in the reference group (P=0.001). The integrity index showed no significant differences between these groups (P=0.258), except for histological type (P=0.012). A higher ccfDNA concentration was also associated with patients younger than 50 years (P=0.030). The ccfDNA concentration showed significant discriminatory power (AUC: 0.854, C.I.: 0.78-0.92, P=0.001) between patients and the reference group and between tumor-node-metastasis (TNM) stages. In conclusion, ccfDNA concentration proves to be a good diagnostic biomarker for CRC patients, whereas the integrity index did not show diagnostic utility.
结直肠癌(CRC)是世界上第三大常见癌症。总体生存率与临床分期有关:分期越晚,生存率越低;因此,需要定期使用新的、侵入性更小且更具特异性的生物标志物进行监测。循环无细胞 DNA(ccfDNA)的浓度和完整性指数已被提出作为 CRC 的潜在诊断和预后生物标志物,然而,不同报告中仍观察到不一致的结果。在这里,我们在墨西哥人群中分析了这些潜在的 CRC 生物标志物。在这项研究中,检查了 124 例散发性 CRC 患者和 37 名健康个体作为参考组。从所有纳入受试者的血浆样本中分离 ccfDNA。通过荧光计测定 ccfDNA 浓度,通过定量 PCR 扩增(qPCR)ALU 序列测定完整性指数(ALU247/ALU115 比值)。结果表明,CRC 患者的 ccfDNA 浓度高于参考组(P=0.001)。这些组之间的完整性指数没有显著差异(P=0.258),除了组织学类型(P=0.012)。ccfDNA 浓度较高也与年龄小于 50 岁的患者相关(P=0.030)。ccfDNA 浓度在患者与参考组之间以及肿瘤-淋巴结-转移(TNM)分期之间具有显著的区分能力(AUC:0.854,CI:0.78-0.92,P=0.001)。总之,ccfDNA 浓度被证明是 CRC 患者的良好诊断生物标志物,而完整性指数没有显示出诊断效用。