在健康个体和患有胰腺癌、结直肠癌、肺癌或卵巢癌的患者中,高度增高的无细胞DNA的起源。
The origin of highly elevated cell-free DNA in healthy individuals and patients with pancreatic, colorectal, lung, or ovarian cancer.
发表日期:2023 Aug 11
作者:
Austin K Mattox, Christopher Douville, Yuxuan Wang, Maria Popoli, Janine Ptak, Natalie Silliman, Lisa Dobbyn, Joy Schaefer, Steve Lu, Alexander H Pearlman, Joshua D Cohen, Jeanne Tie, Peter Gibbs, Kamel Lahouel, Chetan Bettegowda, Ralph H Hruban, Cristian Tomasetti, Peiyong Jiang, K C Allen Chan, Yuk Ming Dennis Lo, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein
来源:
Cancer Discovery
摘要:
癌症患者的血浆游离DNA (cfDNA) 浓度通常比健康对照组高,但该额外cfDNA的来源尚未确定。为了解决这个问题,我们对178名患有结肠癌、胰腺癌、肺癌或卵巢癌的病人和64名无癌症病人进行了cfDNA甲基化模式的评估。这些个体中,83人的cfDNA浓度远高于一般健康人。在所有样本中,cfDNA的主要贡献者是白血球,占cfDNA的约76%,其中以嗜中性粒细胞为主。无论样本是来自癌症患者还是总体血浆cfDNA浓度,这个结果都成立。观察到的高cfDNA水平不来自恶性细胞,也不来自原发肿瘤的周围正常上皮细胞。这些数据表明,癌症可能对细胞更新或DNA清除产生系统性影响。
cfDNA concentrations from patients with cancer are often elevated compared to that of healthy controls, but the sources of this extra cfDNA have never been determined. To address this issue, we assessed cfDNA methylation patterns in 178 patients with cancers of the colon, pancreas, lung, or ovary and 64 patients without cancer. Eighty-three of these individuals had cfDNA concentrations much greater than those generally observed in healthy subjects. The major contributor of cfDNA in all samples was leukocytes, accounting for ~76% of cfDNA, with neutrophils predominating. This was true regardless of whether the samples were derived from patients with cancer or the total plasma cfDNA concentration. High levels of cfDNA observed in patients with cancer did not come from either neoplastic cells or from surrounding normal epithelial cells from the tumor's tissue of origin. These data suggest that cancers may have a systemic effect on cell turnover or DNA clearance.