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首页> 外文期刊>Neoplasia: an international journal for oncology research >Molecular Subtypes of Uterine Leiomyosarcoma and Correlation with Clinical Outcome
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Molecular Subtypes of Uterine Leiomyosarcoma and Correlation with Clinical Outcome

机译：子宫平滑肌肉瘤的分子亚型和与临床结果的相关性

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The molecular etiology of uterine leiomyosarcoma (ULMS) is poorly understood, which accounts for the wide disparity in outcomes among women with this disease. We examined and compared the molecular profiles of ULMS and normal myometrium (NL) to identify clinically relevant molecular subtypes. Discovery cases included 29 NL and 23 ULMS specimens. RNA was hybridized to Affymetrix U133A 2.0 transcription microarrays. Differentially expressed genes and pathways were identified using standard methods. Fourteen NL and 44 ULMS independent archival samples were used for external validation. Molecular subgroups were correlated with clinical outcome. Pathway analyses of differentially expressed genes between ULMS and NL samples identified overrepresentation of cell cycle regulation, DNA repair, and genomic integrity. External validation confirmed differential expression in 31 genes (P & 4.4 × 10?4, Bonferroni corrected), with 84% of the overexpressed genes, including CDC7, CDC20, GTSE1, CCNA2, CCNB1, and CCNB2, participating in cell cycle regulation. Unsupervised clustering of ULMS identified two clades that were reproducibly associated with progression-free (median, 4.0 vs 26.0 months; P = .02; HR, 0.33) and overall (median, 18.2 vs 77.2 months; P = .04; HR, 0.33) survival. Cell cycle genes play a key role in ULMS sarcomagenesis, providing opportunities for therapeutic targeting. Reproducible molecular subtypes associated with clinical outcome may permit individualized adjuvant treatment after clinical trial validation.
机译：子宫平滑肌肉瘤（ULMS）的分子病因尚未理解，这对患有这种疾病的妇女的成果的广泛差异占了。我们检查并比较了ulms和正常myometrium（nl）的分子谱来鉴定临床相关的分子亚型。发现案例包括29个NL和23个ULMS样本。 RNA与Affymetrix U133A 2.0转录微阵列杂交。使用标准方法鉴定差异表达的基因和途径。 14个NL和44 ULMS独立档案样本用于外部验证。分子亚组与临床结果相关。 ulms和Nl样品之间的差异表达基因的通路分析确定了细胞周期调节，DNA修复和基因组完整性的超重。外部验证确认了31个基因中的差异表达（P＆ 4.4×10？4，Bonferroni校正），84％的过表达基因包括CDC7，CDC20，GTSe1，CCNA2，CCNB1和CCNB2，参与细胞周期调节。 Unsvived of Ulms聚类鉴定了两种正在与无进展相关的两种曲线（中位数，4.0 vs 26.0个月; p = .02; hr，0.33）和总体（中位数，18.2与77.2个月; p = .04; hr，0.33 ）生存。细胞周期基因在ulms sarcomagenesis中发挥着关键作用，为治疗靶向提供了机会。与临床结果相关的可重复的分子亚型可允许临床试验后的个体化佐剂治疗。

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