Sávia Raquel Costa Normando, Pamela de Oliveira Delgado, Ana Katherine Soares Barbosa Rodrigues, Waldec Jorge David Filho, Fernando Luiz Affonso Fonseca, Felipe José Silva Melo Cruz, Auro Del Giglio
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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.</p><p><strong>Results: </strong>Patients with advanced gastric cancer had significantly higher concentrations of cfDNA compared with normal controls (<i>p</i> = 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 <i>p</i> = 0.0228).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":35804,"journal":{"name":"BMC Clinical Pathology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2018-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258437/pdf/","citationCount":"0","resultStr":"{\"title\":\"Circulating free plasma tumor DNA in patients with advanced gastric cancer receiving systemic chemotherapy.\",\"authors\":\"Sávia Raquel Costa Normando, Pamela de Oliveira Delgado, Ana Katherine Soares Barbosa Rodrigues, Waldec Jorge David Filho, Fernando Luiz Affonso Fonseca, Felipe José Silva Melo Cruz, Auro Del Giglio\",\"doi\":\"10.1186/s12907-018-0079-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Advanced gastric cancers are usually associated with incurable conditions for which systemic treatments are indicated. 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引用次数: 0
摘要
背景：晚期胃癌通常无法治愈，需要接受系统治疗。最近的研究表明，循环无细胞血浆肿瘤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和监测全身治疗的疗效。我们开展了一项试验性研究，分析tDNA作为生物标志物在晚期胃癌患者中的潜在作用：我们纳入了 30 名局部晚期不可切除或转移性胃癌患者。我们每 3 个月采集一次每位患者的样本（10 mL 全血），并同时进行 CT 检查，直至疾病进展或死亡。使用GeneQuant RNA/DNA Calculator-Amersham Pharmacia Biotech (Biochrom) Ltd.测量无细胞循环DNA（cfDNA）样本总量。cfDNA 用于评估 ALU DNA 序列 247 和 115。tDNA 水平根据 ALU DNA 序列表达量与总细胞游离 DNA 浓度的比值计算得出。我们采用 RECIST 标准 1.1 评估肿瘤反应：结果：与正常对照组相比，晚期胃癌患者的 cfDNA 浓度明显更高（p = 0.00015），因此我们得出结论，患者体内的 cfDNA 来自肿瘤。我们没有发现 tDNA 水平与手术时间或肿瘤反应之间有任何明显的相关性。然而，在第一周期化疗后（3个月），我们观察到，与tDNA水平较高的患者相比，tDNA水平较低的患者的DFS明显较长（Cox回归 p = 0.0228）：化疗开始后 3 个月，tDNA 水平与接受全身化疗的晚期胃癌患者的 DFS 相关。
Circulating free plasma tumor DNA in patients with advanced gastric cancer receiving systemic chemotherapy.
Background: 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.
Methods: 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.
Results: Patients with advanced gastric cancer had significantly higher concentrations of cfDNA compared with normal controls (p = 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 p = 0.0228).
Conclusions: 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.
期刊介绍：
BMC Clinical Pathology is an open access journal publishing original peer-reviewed research articles in all aspects of histopathology, haematology, clinical biochemistry, and medical microbiology (including virology, parasitology, and infection control). BMC Clinical Pathology (ISSN 1472-6890) is indexed/tracked/covered by PubMed, CAS, EMBASE, Scopus and Google Scholar.
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