Clinical Relevance of Alterations in Quantity and Quality of Plasma DNA in Colorectal Cancer Patients: Based on the Mutation Spectra Detected in Primary Tumors
Clinical Relevance of Alterations in Quantity and Quality of Plasma DNA in Colorectal Cancer Patients: Based on the Mutation Spectra Detected in Primary Tumors
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DOI：
10.1245/s10434-014-3804-5
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发表时间：
2014-12-01
影响因子：
3.7
通讯作者：
Chang, Shih-Ching
中科院分区：
文献类型：
--
作者：
Lin, Jen-Kou;Lin, Pei-Ching;Chang, Shih-Ching
背景虽然循环血浆DNA（cpDNA）可能起源于肿瘤，但在不了解肿瘤突变的情况下，其效用有限。本研究评估了原发性肿瘤的突变谱，并阐明了定量和定性cpDNA改变在结直肠癌（CRC）患者中的实用性。在2005年至2006年期间，台北荣民总医院的191名结直肠癌手术患者参加了一项74个基因中155个突变的突变谱研究。采用Taqman qPCR法检测133例患者的cpDNA浓度。测量的终点是手术后的总生存期（OS）。采用log-rank检验和考克斯回归分析确定预后价值。在191例肿瘤中，137例（71.7%）发现17个基因的208个突变。KRAS的突变频率为38.7%，其次是APC（23.0%）、TP 53（19.9%）、PIK 3CA（7.3%）和BRAF（4.2%）。I期、II期和III期患者的中位cpDNA分别为4，300、4，800和5，600拷贝/mL，IV期患者增加至13，000拷贝/mL（p =.003）。在90例发生突变的原发性肿瘤中，I期、II期和III期疾病中cpDNA突变的敏感性分别为24.0%、45.0%和27.3%，IV期增加到87.5%。低cpDNA的CRC患者的5年OS显著优于高cpDNA的患者（p = 0.001）。逐步排除显示cpDNA是OS的一个强预后因子。血浆DNA改变是结直肠癌患者临床监测的有用工具，可能是一个独立的指示剂。
Background. While circulating plasma DNA (cpDNA) likely originates in tumors, its utility is limited without knowledge of tumor mutations. This study assessed mutational spectra in primary tumors and clarified the utility of quantitative and qualitative cpDNA alterations in colorectal cancer (CRC) patients.Materials and Methods. Between 2005 and 2006, 191 surgical colorectal cancer patients at Taipei Veterans General Hospital were enrolled in a study of mutational spectra of 155 mutations in 74 genes. Concentrations of cpDNA in 133 patients were measured by Taqman qPCR. The measured endpoint was overall survival (OS) after surgery. The prognostic value was determined using the log-rank test and Cox regression analysis.Results. Of 191 tumors, 208 mutations in 17 genes were found in 137 tumors (71.7 %). Mutation frequencies were 38.7 % in KRAS, followed by APC (23.0 %), TP53 (19.9 %), PIK3CA (7.3 %), and BRAF (4.2 %). The median cpDNA in stage I, II, and III patients was 4,300, 4,800, and 5,600 copies/mL, respectively, increasing to 13,000 copies/mL in stage IV disease (p =.003). From 90 primary tumors with mutations, the sensitivity of cpDNA mutations were 24.0, 45.0, and 27.3 % in the stage I, II, and III disease, respectively, increasing to 87.5 % in stage IV. The 5-year OS of CRC patients with low cpDNA was significantly better than that of patients with high cpDNA (p =.001). Stepwise elimination showed cpDNA to be a strong prognostic factor for OS.Conclusions. Plasma DNA alteration is a useful tool for clinical surveillance of colorectal cancer patients and might be an independent prognosticator.