Normando Sávia Raquel Costa, Delgado Pamela de Oliveira, Rodrigues Ana Katherine Soares Barbosa, David Filho Waldec Jorge, Fonseca Fernando Luiz Affonso, Cruz Felipe José Silva Melo, Del Giglio Auro
1Discipline of Hematology and Oncology at ABC Foundation School of Medicine, Santo André, Brazil.
2Instituto Brasileiro de Controle do Câncer (IBCC), São Paulo, Brazil.
BMC Clin Pathol. 2018 Nov 26;18:12. doi: 10.1186/s12907-018-0079-y. eCollection 2018.
Advanced gastric cancers are usually associated with incurable conditions for which systemic treatments are indicated. Recent studies suggest that circulating cell-free plasma DNA of tumour origin (tDNA) is a promising non-invasive biomarker that can be used to predict the prognosis and monitor the efficacy of systemic treatments in patients with certain types of cancer. We conducted a pilot study to analyse the potential role of tDNA as a biomarker in patients with advanced gastric cancer.
We included 30 patients with locally advanced unresectable or metastatic gastric cancer. We obtained samples (10 mL of total blood) from each patient every 3 months and performed concomitant CT until disease progression or death. Total cell-free circulating DNA (cfDNA) samples were measured using GeneQuant RNA/DNA Calculator-Amersham Pharmacia Biotech (Biochrom) Ltd. The cfDNA was used to evaluate the ALU DNA sequences 247 and 115. The level of tDNA was calculated from the ratio of the expression of ALU DNA sequences and the concentration of total cell-free DNA. We utilized the RECIST criteria 1.1 to evaluate the tumour response.
Patients with advanced gastric cancer had significantly higher concentrations of cfDNA compared with normal controls ( = 0.00015), which allowed us to conclude that the cfDNA in the patients originated from the tumour. We did not find any significant correlation between the level of tDNA and OS or tumour response. However, after the first cycles of chemotherapy (at 3 months), we observed that patients with lower tDNA levels had significantly longer DFS compared with those with higher levels (Cox Regression = 0.0228).
At 3 months after the beginning of chemotherapy, the tDNA levels are correlated with DFS in patients with advanced gastric cancer who receive systemic chemotherapy. tDNA may be a specific, non-invasive and cost effective new biomarker for these patients.
晚期胃癌通常与无法治愈的病情相关，对此需进行全身治疗。近期研究表明，肿瘤来源的循环游离血浆DNA（tDNA）是一种很有前景的非侵入性生物标志物，可用于预测某些类型癌症患者的预后并监测全身治疗的疗效。我们开展了一项试点研究，以分析tDNA作为晚期胃癌患者生物标志物的潜在作用。
我们纳入了30例局部晚期不可切除或转移性胃癌患者。每3个月从每位患者采集样本（全血10毫升），并同时进行CT检查，直至疾病进展或死亡。使用GeneQuant RNA/DNA计算器（安玛西亚生物科技有限公司，Biochrom）测量总游离循环DNA（cfDNA）样本。cfDNA用于评估ALU DNA序列247和115。根据ALU DNA序列的表达与总游离DNA浓度的比值计算tDNA水平。我们采用实体瘤疗效评价标准（RECIST）1.1来评估肿瘤反应。
与正常对照组相比，晚期胃癌患者的cfDNA浓度显著更高（P = 0.00015），这使我们得出结论，患者的cfDNA源自肿瘤。我们未发现tDNA水平与总生存期或肿瘤反应之间存在任何显著相关性。然而，在化疗的首个周期后（3个月时），我们观察到tDNA水平较低的患者与水平较高的患者相比，无病生存期显著更长（Cox回归，P = 0.0228）。
在化疗开始3个月时，tDNA水平与接受全身化疗的晚期胃癌患者的无病生存期相关。tDNA可能是这些患者一种特异性、非侵入性且具有成本效益的新型生物标志物。
