Noninvasive urinary protein signatures associated with colorectal cancer diagnosis and metastasis.
Noninvasive urinary protein signatures associated with colorectal cancer diagnosis and metastasis.
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与结直肠癌诊断和转移相关的无创尿蛋白特征
DOI：
10.1038/s41467-022-30391-8
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发表时间：
2022-05-19
影响因子：
16.6
通讯作者：
Zhao, Xiaohang
中科院分区：
文献类型：
--
作者：
Sun, Yulin;Guo, Zhengguang;Liu, Xiaoyan;Yang, Lijun;Jing, Zongpan;Cai, Meng;Zheng, Zhaoxu;Shao, Chen;Zhang, Yefan;Sun, Haidan;Wang, Li;Wang, Minjie;Li, Jun;Tian, Lusong;Han, Yue;Zou, Shuangmei;Gao, Jiajia;Zhao, Yan;Nan, Peng;Xie, Xiufeng;Liu, Fang;Zhou, Lanping;Sun, Wei;Zhao, Xiaohang
目前，影像、粪便免疫化学试验(FITS)和血清癌胚抗原(CEA)检测不足以对结直肠癌(CRC)的转移和复发进行早期发现和评估。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例尿液和993例有明显转移风险的健康对照和结直肠癌患者的组织样本中实施了阶段性发现-验证-验证流水线。生成的诊断特征结合FIT测试显示，与单独FIT相比，敏感度显著提高(训练集+21.2%，验证集+43.7%)。此外，风险分层所产生的转移标志可正确预测50%以上CEA阴性的转移患者。组织验证表明，尿蛋白生物标志物升高反映了它们在组织中的变化。在这里，我们展示了有希望的尿蛋白信号，并提供了潜在的介入靶点来可靠地检测结直肠癌，尽管需要进一步的多中心外部验证来推广这些发现。对于癌症的早期检测，需要更敏感和更特异的非侵入性生物标志物。在这里，作者展示了尿液中的蛋白质特征，当结合粪便免疫化学测试时，提高了结直肠癌检测的敏感性，并在一些粪便免疫化学测试阴性的患者中纠正了诊断。
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. More sensitive and specific non-invasive biomarkers are desired for early detection of cancer. Here, the authors show a protein signature in the urine that increases sensitivity for colorectal cancer detection when combined with fecal immunochemical tests and corrects diagnosis in some fecal immunochemical tests-negative patients.
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