Oncosuppressor-Mutated Cell-Based Diagnostic Platform for Liquid Biopsy Diagnoses Benign Head and Neck Masses and Predicts Malignancy in Thyroid Nodules: Results from a Consecutive Cohort of Patients
Oncosuppressor-Mutated Cell-Based Diagnostic Platform for Liquid Biopsy Diagnoses Benign Head and Neck Masses and Predicts Malignancy in Thyroid Nodules: Results from a Consecutive Cohort of Patients
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DOI：
10.1159/000516421
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发表时间：
2021-06-07
影响因子：
4.7
通讯作者：
Arena, Goffredo Orazio
中科院分区：
文献类型：
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作者：
Abdouh, Mohamed;Tabah, Roger;Arena, Goffredo Orazio
背景：我们报道了一种基于肿瘤抑制突变细胞（OMC）的新型平台，具有对健康个体进行早期癌症检测和识别有异时转移风险的癌症患者的潜力。目的：在此，我们试图确定这种基于 OMC 的新型平台在连续队列中对可疑头颈部肿块进行手术的患者的诊断准确性。方法：在手术切除前，将 OMC（BRCA1 缺陷型成纤维细胞）暴露于头颈部结节患者的血清中。分析这些细胞的增殖和存活。将处理过的 OMC 皮下接种到 NOD/SCID 小鼠中，并随时间监测肿瘤生长。结果：与暴露于良性病变患者血清的 OMC 相比，暴露于恶性病变患者血清的 OMC 表现出增殖增加。只有暴露于诊断为恶性甲状腺肿瘤患者血清的 OMC 才会产生癌性肿块。该测试的敏感性为 92%，34 名患者中只有 1 名假阴性。免疫组织化学染色显示癌肿块为低分化腺癌，增殖指数高。结论：这些数据表明，液体活检结合基于 OMC 的体内平台具有诊断良性头颈部肿块并预测甲状腺结节是否恶性的潜力。这些结果强化了 OMC 可用于检测癌症患者循环恶性因子的概念。
Background: We reported that a novel oncosuppressor-mutated cell (OMC)-based platform has the potential for early cancer detection in healthy individuals and for identification of cancer patients at risk of developing metachronous metastases. Objective: Herein, we sought to determine the diagnostic accuracy of this novel OMC-based platform in a consecutive cohort of patients operated for suspicious head and neck masses. Methods: OMCs (BRCA1-deficient fibroblasts) were exposed to blood serum from patients with head and neck nodules before surgical removal. These cells were analyzed for their proliferation and survival. Treated OMCs were inoculated subcutaneously in NOD/SCID mice, and tumor growth was monitored over time. Results: OMCs exposed to serum from patients with malignant lesions displayed increased proliferation compared to those exposed to serum from patients with benign lesions. Only OMCs exposed to serum from patients diagnosed with malignant thyroid neoplasia generated a cancerous mass. The sensitivity of the test was 92%, with only 1 false negative out of 34 patients. Immunohistochemical staining showed that the cancerous masses were poorly differentiated adenocarcinomas with high proliferative index. Conclusions: These data show that liquid biopsy combined with an OMC-based in vivo platform has the potential to diagnose benign head and neck masses and predict whether a thyroid nodule is malignant. These results strengthen the concept that OMCs can be used to detect circulating malignant factors in cancer patients.