Nevisi Fatemeh, Yaghmaie Marjan, Pashaiefar Hossein, Alimoghaddam Kamran, Iravani Masoud, Javadi Gholamreza, Ghavamzadeh Ardeshir
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Hematology, Oncology and Stem cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Iran Biomed J. 2020 Jan;24(1):47-53. doi: 10.29252/ibj.24.1.47. Epub 2019 Aug 28.
The analysis of the gene copy number alterations in tumor samples are increasingly used for diagnostic and prognostic purposes in patients with gastric cancer (GC). However, these procedures are not always applicable due to their invasive nature. In this study, we have analyzed the copy number alterations of five genes (HER2, MDM2, c-MYC, c-MET, and TP53) with a fixed relevance for GC in the circulating tumor cells (CTCs) of GC patients, and, accordingly, as a potential approach, evaluated their usage to complete primary tumor biopsy.
We analyzed the status of the copy number alterations of the selected genes in CTCs and matched biopsy tissues from 37 GC patients using fluorescence in situ hybridization.
HER2 amplification was observed in 2 (5.41%) samples. HER2 gene status in CTCs showed a strong agreement with its status in 36 out of 37 patients’ matched tissue samples (correlation: 97.29%; Kappa: 0.65; p < 0.001). MDM2 amplification was found only in 1 (2.70%) sample; however, the amplification of this gene was not detectable in the CTCs isolated from this patient. c-MYC amplification was observed in 3 (8.11%) samples, and the status of its amplification in the CTCs indicated a complete agreement with its status in the matched tissue samples (correlation: 100%; Kappa: 1.0).
Our work suggests that the amplification of HER2 and c-MYC is in concordance with the CTCs and achieved biopsies, and, consequently, CTCs may act as a non-invasive alternative for recording the amplification of these genes among GC patients.
肿瘤样本中基因拷贝数改变的分析越来越多地用于胃癌（GC）患者的诊断和预后评估。然而，由于其侵入性，这些方法并非总是适用。在本研究中，我们分析了胃癌患者循环肿瘤细胞（CTC）中五个与胃癌有固定相关性的基因（HER2、MDM2、c-MYC、c-MET和TP53）的拷贝数改变，并据此评估它们作为完成原发性肿瘤活检的潜在方法的应用。
我们使用荧光原位杂交分析了37例GC患者CTC和匹配活检组织中所选基因的拷贝数改变状态。
在2个（5.41%）样本中观察到HER2扩增。CTC中的HER2基因状态与其在37例患者中36例匹配组织样本中的状态高度一致（相关性：97.29%；Kappa值：0.65；p<0.001）。仅在1个（2.70%）样本中发现MDM2扩增；然而，从该患者分离的CTC中未检测到该基因的扩增。在3个（8.11%）样本中观察到c-MYC扩增，其在CTC中的扩增状态与其在匹配组织样本中的状态完全一致（相关性：100%；Kappa值：1.0）。
我们的研究表明，HER2和c-MYC的扩增与CTC及获得的活检结果一致，因此，CTC可作为GC患者中记录这些基因扩增的非侵入性替代方法。
