You Hye Jin, Park Ho-Young, Kim Jinkuk, Lee In-Hee, Seol Ho Jun, Lee Jung-Il, Kim Sung Tae, Kong Doo-Sik, Nam Do-Hyun
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea Departments of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea Samsung Advanced Institute of Technology, Samsung Electronics Co. Ltd., Seoul, Korea Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Medicine (Baltimore). 2016 Jul;95(27):e4109. doi: 10.1097/MD.0000000000004109.
Despite therapeutic advances, the prognosis for glioblastoma (GBM) remains poor. In particular, leptomeningeal dissemination (LMD) has a dismal prognosis. The aim of this study was to identify tumor molecular phenotype, which has a great propensity to develop LMD. Between May 2004 and December 2012, a total of 145 GBM tumor samples were obtained from data registry. A total of 20 of the 145 patients with GBM were found to develop LMD. A specialized radiologist confirmed the diagnosis of LMD on magnetic resonance imaging. To clarify the genomic signatures in GBM with LMD, we performed integrative analysis of whole transcriptome sequencing and copy number alteration in the radiological features indicating LMD phenotypes in GBM. Eleven newly diagnosed patients with GBM with LMD had worse prognosis than those without LMD (median 5.55 vs. 12.94 months, P < 0.0001). Integrating analysis using gene expression based on the change of copy number revealed that SPOCK1, EHD2, SLC2A3, and ANXA11 were highly expressed with the gain of copy number, compared with the gene expression in the non-LMD group. In addition, it was demonstrated that NME2, TMEM100, and SIVA1 were downregulated with the loss of copy number. We also found that mesenchymal subtype accounted for 50% in LMD group, whereas mesenchymal subtype consisted of 29% in non-LMD group, even though there was no statistical significance (P = 0.06). Through this radiogenomic analysis, we suggested the possibility of finding candidate genes associated with LMD and highlighted the significance of integrating approach to clarify the molecular characteristics in LMD.
尽管治疗取得了进展，但胶质母细胞瘤（GBM）的预后仍然很差。特别是软脑膜播散（LMD）的预后很糟糕。本研究的目的是确定极易发生LMD的肿瘤分子表型。在2004年5月至2012年12月期间，从数据登记处共获取了145份GBM肿瘤样本。在145例GBM患者中，共有20例发生了LMD。一名专业放射科医生通过磁共振成像确认了LMD的诊断。为了阐明GBM合并LMD的基因组特征，我们对全转录组测序和拷贝数改变进行了综合分析，这些改变存在于显示GBM中LMD表型的放射学特征中。11例新诊断的GBM合并LMD患者的预后比未发生LMD的患者更差（中位生存期分别为5.55个月和12.94个月，P<0.0001）。基于拷贝数变化的基因表达综合分析显示，与非LMD组的基因表达相比，SPOCK1、EHD2、SLC2A3和ANXA11在拷贝数增加时高表达。此外，还证明NME2、TMEM100和SIVA1在拷贝数缺失时表达下调。我们还发现，间充质亚型在LMD组中占50%，而在非LMD组中占29%，尽管没有统计学意义（P = 0.06）。通过这种放射基因组分析，我们提出了找到与LMD相关的候选基因的可能性，并强调了采用综合方法阐明LMD分子特征的重要性。
