Classification of High-Grade Serous Ovarian Carcinoma by Epithelial-to-Mesenchymal Transition Signature and Homologous Recombination Repair Genes

被引:11
|
作者
Sohn, Min-Hwan [1 ,2 ,3 ]
Kim, Se Ik [4 ]
Shin, Jong-Yeon [2 ]
Kim, Hee Seung [4 ]
Chung, Hyun Hoon [4 ]
Kim, Jae-Weon [4 ]
Lee, Maria [4 ,5 ]
Seo, Jeong-Sun [1 ,2 ,3 ,6 ]
机构
[1] Seoul Natl Univ, Bundang Hosp, Precis Med Ctr, Seongnam Si 13605, South Korea
[2] Macrogen Inc, Precis Med Inst, Seongnam Si 13605, South Korea
[3] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul 03080, South Korea
[4] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 03080, South Korea
[5] Seoul Natl Univ Hosp, Dept Obstet & Gynecol, Seoul 03080, South Korea
[6] Gong Wu Genom Med Inst, Seongnam Si 13605, South Korea
基金
新加坡国家研究基金会;
关键词
ovarian cancer; high-grade serous carcinoma; gene signature; epithelial-to-mesenchymal transition; homologous recombination repair; DOUBLE-BLIND; CANCER; BREAST; THERAPY; BRCA1;
D O I
10.3390/genes12071103
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
High-grade serous ovarian cancer (HGSOC) is one of the deadliest cancers that can occur in women. This study aimed to investigate the molecular characteristics of HGSOC through integrative analysis of multi-omics data. We used fresh-frozen, chemotherapy-naive primary ovarian cancer tissues and matched blood samples of HGSOC patients and conducted next-generation whole-exome sequencing (WES) and RNA sequencing (RNA-seq). Genomic and transcriptomic profiles were comprehensively compared between patients with germline BRCA1/2 mutations and others with wild-type BRCA1/2. HGSOC samples initially divided into two groups by the presence of germline BRCA1/2 mutations showed mutually exclusive somatic mutation patterns, yet the implementation of high-dimensional analysis of RNA-seq and application of epithelial-to-mesenchymal (EMT) index onto the HGSOC samples revealed that they can be divided into two subtypes; homologous recombination repair (HRR)-activated type and mesenchymal type. Patients with mesenchymal HGSOC, characterized by the activation of the EMT transcriptional program, low genomic alteration and diverse cell-type compositions, exhibited significantly worse overall survival than did those with HRR-activated HGSOC (p = 0.002). In validation with The Cancer Genome Atlas (TCGA) HGSOC data, patients with a high EMT index (>= the median) showed significantly worse overall survival than did those with a low EMT index (<the median) (p = 0.030). In conclusion, through a comprehensive multi-omics approach towards our HGSOC cohorts, two distinctive types of HGSOC (HRR-activated and mesenchymal) were identified. Our novel EMT index seems to be a potential prognostic biomarker for HGSOC.
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页数:16
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