循环肿瘤无细胞DNA基因作为铂耐药卵巢癌诊断的预后基因标志。

IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Biomarker Insights Pub Date : 2022-01-01 DOI:10.1177/11772719221088404
Camille C Gunderson, Rangasudhagar Radhakrishnan, Rohini Gomathinayagam, Sanam Husain, Sheeja Aravindan, Kathleen M Moore, Danny N Dhanasekaran, Muralidharan Jayaraman
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引用次数: 1

摘要

妇科癌症的临床治疗从一线铂类化疗开始。然而,在约80%的患者中,卵巢癌会复发并且是致命的。预后基因标记面板识别铂耐药,使患者更好地分层进行精确治疗。回顾性收集11例预后不良(24个月PFI)患者的血清,采用循环无细胞DNA (cfDNA)进行评估。两组DNA均显示50 ~ 10000 bp的片段。对患者cfDNA测序的两两分析显示,在预后较差的患者中,29个基因的剂量较高,64个基因的剂量较低。高剂量基因主要分为细胞骨架蛋白,低剂量基因主要分为水解酶和受体。在Reactome数据库中搜索高剂量基因,发现有15个基因与癌症相关。其中TGFBR2、ZMIZ2、NRG2 3个基因与4个以上癌症相关基因相互作用。肿瘤样本蛋白表达分析显示,在预后不良患者中,TGFBR2下调,ZMIZ2上调。我们的研究结果表明,cfDNA基因剂量结合肿瘤样品中的蛋白表达可以作为卵巢癌患者预后判断的基因标记面板。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Circulating Tumor Cell-Free DNA Genes as Prognostic Gene Signature for Platinum Resistant Ovarian Cancer Diagnosis.

Clinical management of gynecological cancer begins by optimal debulking with first-line platinum-based chemotherapy. However, in ~80% patients, ovarian cancer will recur and is lethal. Prognostic gene signature panel identifying platinum-resistance enables better patient stratification for precision therapy. Retrospectively collected serum from 11 "poor" (<6 months progression free interval [PFI]) and 22 "favorable" (>24 months PFI) prognosis patients, were evaluated using circulating cell-free DNA (cfDNA). DNA from both groups showed 50 to 10 000 bp fragments. Pairwise analysis of sequenced cfDNA from patients showed that gene dosages were higher for 29 genes and lower for 64 genes in poor than favorable prognosis patients. Gene ontology analysis of higher dose genes predominantly grouped into cytoskeletal proteins, while lower dose genes, as hydrolases and receptors. Higher dosage genes searched for cancer-relatedness in Reactome database indicated 15 genes were referenced with cancer. Among them 3 genes, TGFBR2, ZMIZ2, and NRG2, were interacting with more than 4 cancer-associated genes. Protein expression analysis of tumor samples indicated that TGFBR2 was downregulated and ZMIZ2 was upregulated in poor prognosis patients. Our results indicate that the cfDNA gene dosage combined with protein expression in tumor samples can serve as gene signature panel for prognosis determination amongst ovarian cancer patients.

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来源期刊
Biomarker Insights
Biomarker Insights MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.00
自引率
0.00%
发文量
26
审稿时长
8 weeks
期刊介绍: An open access, peer reviewed electronic journal that covers all aspects of biomarker research and clinical applications.
期刊最新文献
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