Liquid biopsy reveals collateral tissue damage in cancer.
Liquid biopsy reveals collateral tissue damage in cancer.
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DOI：
10.1172/jci.insight.153559
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发表时间：
2022-01-25
期刊：
影响因子：
8
通讯作者：
Dor Y
中科院分区：
文献类型：
--
作者：
Lubotzky A;Zemmour H;Neiman D;Gotkine M;Loyfer N;Piyanzin S;Ochana BL;Lehmann-Werman R;Cohen D;Moss J;Magenheim J;Loftus MF;Brais L;Ng K;Mostoslavsky R;Wolpin BM;Zick A;Maoz M;Grinshpun A;Kustanovich A;Makranz C;Cohen JE;Peretz T;Hubert A;Temper M;Salah A;Avniel-Polak S;Grozinsky-Glasberg S;Spalding KL;Rokach A;Kaplan T;Glaser B;Shemer R;Dor Y
癌症会对周围正常组织造成损害，最终导致致命的器官衰竭。在这里，我们证明受癌症影响的器官中的细胞死亡可以通过循环游离 DNA (cfDNA) 的组织特异性甲基化模式来检测。与无肝转移的癌症患者相比，我们检测到来自不同原发肿瘤的肝转移患者血浆中肝细胞衍生的 cfDNA 水平升高。此外，局限性胰腺癌或结肠癌患者的肝细胞cfDNA升高，表明微转移性疾病、原发性胰腺肿瘤压迫胆管或对原发性肿瘤的全身反应造成肝损伤。我们还发现，与没有脑转移的癌症患者相比，脑转移患者亚群中神经元、少突胶质细胞和星形胶质细胞衍生的 cfDNA 升高。细胞类型特异性 cfDNA 甲基化标记物能够识别癌症中的附带组织损伤，揭示特定位置转移的存在，并可能有助于早期癌症检测。
Cancer inflicts damage to surrounding normal tissues, which can culminate in fatal organ failure. Here, we demonstrate that cell death in organs affected by cancer can be detected by tissue-specific methylation patterns of circulating cell-free DNA (cfDNA). We detected elevated levels of hepatocyte-derived cfDNA in the plasma of patients with liver metastases originating from different primary tumors, compared with cancer patients without liver metastases. In addition, patients with localized pancreatic or colon cancer showed elevated hepatocyte cfDNA, suggesting liver damage inflicted by micrometastatic disease, by primary pancreatic tumor pressing the bile duct, or by a systemic response to the primary tumor. We also identified elevated neuron-, oligodendrocyte-, and astrocyte-derived cfDNA in a subpopulation of patients with brain metastases compared with cancer patients without brain metastasis. Cell type–specific cfDNA methylation markers enable the identification of collateral tissue damage in cancer, revealing the presence of metastases in specific locations and potentially assisting in early cancer detection.