Engqvist Hanna, Parris Toshima Z, Rönnerman Elisabeth Werner, Söderberg Elin M V, Biermann Jana, Mateoiu Claudia, Sundfeldt Karin, Kovács Anikó, Karlsson Per, Helou Khalil
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Sahlgrenska University Hospital, Department of Clinical Pathology and Genetics, Gothenburg, Sweden.
Oncotarget. 2018 Oct 12;9(80):35162-35180. doi: 10.18632/oncotarget.26225.
Ovarian cancer is the most lethal gynecological malignancy in the western world. Despite recent efforts to characterize ovarian cancer using molecular profiling, few targeted treatment options are currently available. Here, we examined genetic variants, fusion transcripts, SNP genotyping, and gene expression patterns for early-stage (I and II) ovarian carcinomas (n=96) in relation to clinicopathological characteristics and clinical outcome, thereby identifying novel genetic features of ovarian carcinomas. Furthermore, mutation frequencies of specific genetic variants and/or their gene expression patterns were associated with histotype and overall survival, (mucinous ovarian carcinoma histotype), (low expression in 0-2 year survival group), and tumor suppressor (mutation status and overall survival). The long non-coding RNA was identified as a highly promiscuous fusion transcript in ovarian carcinoma. Moreover, gene expression deregulation for 23 genes was associated with tumor aggressiveness. Taken together, the novel biomarkers identified here may improve ovarian carcinoma subclassification and patient stratification according to histotype and overall survival.
卵巢癌是西方世界最致命的妇科恶性肿瘤。尽管最近致力于通过分子谱分析来表征卵巢癌，但目前可用的靶向治疗方案很少。在此，我们研究了早期（I期和II期）卵巢癌（n = 96）的基因变异、融合转录本、单核苷酸多态性基因分型和基因表达模式，以了解其与临床病理特征和临床结局的关系，从而确定卵巢癌的新遗传特征。此外，特定基因变异的突变频率和/或其基因表达模式与组织学类型和总生存期相关，（黏液性卵巢癌组织学类型），（在0 - 2年生存组中低表达），以及肿瘤抑制因子（突变状态和总生存期）。长链非编码RNA被鉴定为卵巢癌中一种高度混杂的融合转录本。此外，23个基因的基因表达失调与肿瘤侵袭性相关。综上所述，这里鉴定出的新生物标志物可能会根据组织学类型和总生存期改善卵巢癌的亚分类和患者分层。
