State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Proteomics Research Center, Core Facility of Instruments, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Nat Commun. 2022 May 19;13(1):2757. doi: 10.1038/s41467-022-30391-8.
Currently, imaging, fecal immunochemical tests (FITs) and serum carcinoembryonic antigen (CEA) tests are not adequate for the early detection and evaluation of metastasis and recurrence in colorectal cancer (CRC). To comprehensively identify and validate more accurate noninvasive biomarkers in urine, we implement a staged discovery-verification-validation pipeline in 657 urine and 993 tissue samples from healthy controls and CRC patients with a distinct metastatic risk. The generated diagnostic signature combined with the FIT test reveals a significantly increased sensitivity (+21.2% in the training set, +43.7% in the validation set) compared to FIT alone. Moreover, the generated metastatic signature for risk stratification correctly predicts over 50% of CEA-negative metastatic patients. The tissue validation shows that elevated urinary protein biomarkers reflect their alterations in tissue. Here, we show promising urinary protein signatures and provide potential interventional targets to reliably detect CRC, although further multi-center external validation is needed to generalize the findings.
目前，影像学、粪便免疫化学检测（FIT）和血清癌胚抗原（CEA）检测均不足以用于早期发现和评估结直肠癌（CRC）的转移和复发。为了全面识别和验证尿液中更准确的非侵入性生物标志物，我们在 657 份尿液和 993 份来自健康对照者和具有不同转移风险的 CRC 患者的组织样本中实施了分阶段的发现-验证-验证管道。与 FIT 单独使用相比，生成的诊断特征与 FIT 联合使用可显著提高检测的灵敏度（在训练集中增加 21.2%，在验证集中增加 43.7%）。此外，用于风险分层的生成的转移特征可以正确预测超过 50%的 CEA 阴性转移性患者。组织验证表明，尿液中升高的蛋白质生物标志物反映了其在组织中的变化。在这里，我们展示了有前途的尿液蛋白质特征，并提供了潜在的干预靶点，以可靠地检测 CRC，尽管需要进一步的多中心外部验证来推广这些发现。
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