Chou Wei-Chun, Cheng An-Lin, Brotto Marco, Chuang Chun-Yu
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan.
BMC Genomics. 2014 Apr 23;15:300. doi: 10.1186/1471-2164-15-300.
Endometrial cancers (ECs) are the most common form of gynecologic malignancy. Recent studies have reported that ECs reveal distinct markers for molecular pathogenesis, which in turn is linked to the various histological types of ECs. To understand further the molecular events contributing to ECs and endometrial tumorigenesis in general, a more precise identification of cancer-associated molecules and signaling networks would be useful for the detection and monitoring of malignancy, improving clinical cancer therapy, and personalization of treatments.
ECs-specific gene co-expression networks were constructed by differential expression analysis and weighted gene co-expression network analysis (WGCNA). Important pathways and putative cancer hub genes contribution to tumorigenesis of ECs were identified. An elastic-net regularized classification model was built using the cancer hub gene signatures to predict the phenotypic characteristics of ECs. The 19 cancer hub gene signatures had high predictive power to distinguish among three key principal features of ECs: grade, type, and stage. Intriguingly, these hub gene networks seem to contribute to ECs progression and malignancy via cell-cycle regulation, antigen processing and the citric acid (TCA) cycle.
The results of this study provide a powerful biomarker discovery platform to better understand the progression of ECs and to uncover potential therapeutic targets in the treatment of ECs. This information might lead to improved monitoring of ECs and resulting improvement of treatment of ECs, the 4th most common of cancer in women.
子宫内膜癌(ECs)是妇科恶性肿瘤最常见的形式。最近的研究报告称,ECs揭示了分子发病机制的独特标志物,而这又与ECs的各种组织学类型相关。为了进一步了解导致ECs和一般子宫内膜肿瘤发生的分子事件,更精确地识别癌症相关分子和信号网络将有助于恶性肿瘤的检测和监测、改善临床癌症治疗以及实现治疗的个性化。
通过差异表达分析和加权基因共表达网络分析(WGCNA)构建了ECs特异性基因共表达网络。确定了对ECs肿瘤发生有重要贡献的途径和假定的癌症枢纽基因。利用癌症枢纽基因特征建立了弹性网正则化分类模型,以预测ECs的表型特征。这19个癌症枢纽基因特征对区分ECs的三个关键主要特征具有很高的预测能力:分级、类型和分期。有趣的是,这些枢纽基因网络似乎通过细胞周期调控、抗原加工和柠檬酸(TCA)循环促进ECs的进展和恶性转化。
本研究结果提供了一个强大的生物标志物发现平台,以更好地了解ECs的进展并揭示ECs治疗中的潜在治疗靶点。这些信息可能会改善对ECs的监测,并进而改善对ECs的治疗,ECs是女性中第四常见的癌症。