Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan,
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.
Digestion. 2019;99(1):39-45. doi: 10.1159/000494411. Epub 2018 Dec 14.
Liquid biopsy is a collective term that refers to the analysis of tumor-derived biomarkers isolated from biological fluids of cancer patients. Recently, many authors reported the usefulness of liquid biopsy for the management of malignancy. Summary and Key Messages: The peripheral blood of cancer patients is a pool of cells and/or cell products derived from the primary or metastatic tumor, including circulating tumor cells (CTCs), circulating free (cf) DNA or RNA, and exosomes containing proteins, nucleic acids, and lipids. CTCs are tumor cells that can be isolated from peripheral blood. Free circulating DNA with a tumor-specific mutation is called circulating tumor DNA (ctDNA). Some patients who undergo curative surgery experience recurrent disease, which can be due to the presence of minimal residual disease (MRD). Thus, MRD indicates a high risk of relapse. Detection of ctDNA or CTC after surgery is a direct proof of MRD. Molecular volume (e.g., the number of CTCs and level of ctDNA) might reflect tumor burden, thus high molecular volume may indicate poor prognosis. The most notable application of liquid biopsy in cancer is to understand spatial and temporal heterogeneities. Heterogeneity is one of the causes of refractoriness and hampers prediction of chemotherapeutic effect. Emerging mutations that are not present in primary tumors but are found in their metastases can be detected in ctDNA. Some colorectal cancer patients with wild-type RAS do not respond to epidermal growth factor receptor blockade. In a subset of these patients, RAS mutation is detected in ctDNA, indicating heterogeneity.
液体活检是一个术语，是指从癌症患者的生物体液中分离出肿瘤来源的生物标志物进行分析。最近，许多作者报告了液体活检在恶性肿瘤管理中的有用性。
癌症患者的外周血是一种源自原发性或转移性肿瘤的细胞和/或细胞产物的池，包括循环肿瘤细胞（CTC）、游离循环（cf）DNA 或 RNA，以及含有蛋白质、核酸和脂质的外泌体。CTC 是可以从外周血中分离出来的肿瘤细胞。具有肿瘤特异性突变的游离循环 DNA 称为循环肿瘤 DNA（ctDNA）。一些接受根治性手术的患者会出现疾病复发，这可能是由于存在微小残留病（MRD）所致。因此，MRD 表明复发风险高。手术后检测 ctDNA 或 CTC 是 MRD 的直接证据。分子体积（例如，CTC 数量和 ctDNA 水平）可能反映肿瘤负担，因此高分子体积可能预示预后不良。液体活检在癌症中的最显著应用是了解空间和时间异质性。异质性是耐药性的原因之一，阻碍了对化疗效果的预测。在 ctDNA 中可以检测到原发肿瘤中不存在但在转移灶中存在的新兴突变。一些野生型 RAS 的结直肠癌患者对表皮生长因子受体阻断剂无反应。在这些患者的亚组中，ctDNA 中检测到 RAS 突变，表明存在异质性。
