White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer.

白细胞和无细胞 DNA 分析检测胃癌残留病。

  • 影响因子:12.19
  • DOI:10.1038/s41467-020-14310-3
  • 作者列表:"Leal A","van Grieken NCT","Palsgrove DN","Phallen J","Medina JE","Hruban C","Broeckaert MAM","Anagnostou V","Adleff V","Bruhm DC","Canzoniero JV","Fiksel J","Nordsmark M","Warmerdam FARM","Verheul HMW","van Spronsen DJ","Beerepoot LV","Geenen MM","Portielje JEA","Jansen EPM","van Sandick J","Meershoek-Klein Kranenbarg E","van Laarhoven HWM","van der Peet DL","van de Velde CJH","Verheij M","Fijneman R","Scharpf RB","Meijer GA","Cats A","Velculescu VE
  • 发表时间:2020-01-27

:Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis. Here, we identify circulating tumor-derived DNA (ctDNA) alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative treatment in patients with operable gastric cancer. After filtering alterations from matched white blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment. These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.


: 液体活检为术后无细胞 DNA (cfDNA) 中残留疾病的检测提供了新的机会,但可能通过鉴定克隆性造血引起的改变而混淆。在此,我们通过对同一患者匹配的 cfDNA 和白细胞进行超灵敏的靶向测序分析,确定循环肿瘤来源的 DNA (ctDNA) 改变。我们应用这种方法分析来自 criters 试验患者的样本,这是一项可手术胃癌患者围手术期治疗的 III 期随机对照研究。过滤匹配白细胞的改变后,ctDNA 的存在可预测术前治疗后 9 周内和术后符合多模式治疗条件的患者的复发。这些分析为区分 ctDNA 与其他 cfDNA 改变提供了一种简便的方法,并突出了 ctDNA 作为患者预后的预测生物标志物对胃癌患者围手术期癌症治疗和手术切除的效用。



作者列表:["Xie W","Chen C","Han Z","Huang J","Liu X","Chen H","Zhang T","Chen S","Chen C","Lu M","Shen X","Xue X"]

METHODS::Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2-associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F-actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.

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作者列表:["Jing JJ","Li H","Wang ZY","Zhou H","Sun LP","Yuan Y"]

METHODS::Aim: To identify the methylated-differentially expressed genes (MDEGs) that may serve as diagnostic markers and therapeutic targets in Epstein-Barr virus-associated gastric cancer (EBVaGC) and to explore the methylation-based pathways for elucidating biological mechanisms of EBVaGC. Materials & methods: Gene expression and methylation profiles were downloaded from GEO database. MDEGs were identified by GEO2R. Pathway enrichment analyses were conducted based on DAVID database. Hub genes were identified by Cytoscape, which were further verified by The Cancer Genome Atlas database. Results: A total of 367 hypermethylated, lowly expressed genes were enriched in specific patterns of cell differentiation. 31 hypomethylated, highly expressed genes demonstrated enrichment in regulation of immune system process. After validation using The Cancer Genome Atlas database, seven genes were confirmed to be significantly different hub genes in EBVaGC. Conclusion: EBVaGC-specific MDEGs and pathways can be served as potential biomarkers for precise diagnosis and treatment of EBVaGC and provide novel insights into the mechanisms involved.

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作者列表:["Daryabari SS","Fathi M","Mahdavi M","Moaddab Y","Hosseinpour Feizi MA","Shokoohi B","Safaralizadeh R"]

METHODS:Gastric adenocarcinoma, like other cancers, is a multifactorial genetic disease, andmetastasis of cancer cells is one of the main features of this illness. The expressionlevels of the CFL1 gene have been modulated in this pathway. Using small interferingRNA (siRNA) in the treatment of gastric cancer is considered a hopeful genetherapeutic approach. The present study reported the level of CFL1 genes betweentumor and margin and healthy tissue of gastric cancer. Also, the features of a cationicnanoparticle with a polymer coating containing polyacrylic acid and polyethylenei-mine that were used in the delivery of CFL1 siRNA, were shown. Then thecytotoxicity, cellular uptake, and gene silencing efficiency of this nanoparticle wereevaluated with CFL1siRNA. Method:In this study, the CFL1 gene expression was measured in 40 gastricadenocarcinoma, marginal and 15 healthy biopsy samples by a real‐time polymerasechain reaction. Physicochemical characteristics, apoptosis, and inhibition of migrationof the delivery of CFL1 siRNA by nanoparticle and lipofectamine were investigated ingastric cancer cells. Result:The CFL1 expression was remarkably increased in gastric cancer tissues incomparison with the marginal samples and normal tissues (p< .05) and the biomarkerindex for CFL1 was obtained as 0.94, then this gene can be probably used as abiomarker for gastric cancer. After treatment of the AGS cell line by CFL1 siRNA, theCFL1 expression level of mRNA and migration in AGS cells were remarkablysuppressed after transfection. Furthermore, the amount of apoptosis increased(p< .05). Conclusion:Our results demonstrated that CFL1 downregulation in AGS cells caninterdict cell migration. Finally, our outcomes propose that CFL1 can function as anoncogenic gene in gastric cancer and would be considered as a potential purpose ofgene therapy for gastric cancer treatment

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