AMPKα modulation in cancer progression: multilayer integrative analysis of the whole transcriptome in Asian gastric cancer.
AMPKα modulation in cancer progression: multilayer integrative analysis of the whole transcriptome in Asian gastric cancer.
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DOI：
10.1158/0008-5472.can-11-3870
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发表时间：
2012-05-15
期刊：
影响因子：
11.2
通讯作者：
Powis G
中科院分区：
文献类型：
--
作者：
Kim YH;Liang H;Liu X;Lee JS;Cho JY;Cheong JH;Kim H;Li M;Downey TJ;Dyer MD;Sun Y;Sun J;Beasley EM;Chung HC;Noh SH;Weinstein JN;Liu CG;Powis G
胃癌是亚洲和大多数发展中国家最常见的癌症。尽管使用了多种治疗方法，但它仍然是世界上癌症死亡的第二大原因。为了确定亚洲人群中胃癌的分子基础，我们对胃癌和非癌标本应用了RNA测序方法，产生了6.8亿个信息性短读数来定量描述胃癌的整个转录组(包括mRNAs和microRNAs)。然后进行多层分析，以确定与不同阶段的胃癌相关的多种类型的转录异常，包括差异表达的mRNAs、反复出现的体细胞突变和关键的差异表达的microRNAs。通过这种方法，我们确定了中枢代谢调节因子AMPK-α是亚洲胃癌的潜在功能靶点。此外，我们在实验中证明了该基因作为亚洲患者早期胃癌潜在治疗靶点的翻译相关性。综上所述，我们的发现不仅为识别和阐明亚洲胃癌的分子机制提供了有价值的信息资源，而且代表了开发更有效的治疗靶点的总体综合框架。
Gastric cancer is the most common cancer in Asia and most developing countries. Despite the use of multimodality therapeutics, it remains the second leading cause of cancer death in the world. To identify the molecular underpinnings of gastric cancer in the Asian population, we applied an RNA-sequencing approach to gastric tumor and noncancerous specimens, generating 680 million informative short reads to quantitatively characterize the entire transcriptome of gastric cancer (including mRNAs and microRNAs). A multi-layer analysis was then developed to identify multiple types of transcriptional aberrations associated with different stages of gastric cancer, including differentially expressed mRNAs, recurrent somatic mutations and key differentially expressed microRNAs. Through this approach, we identified the central metabolic regulator AMPK-α as a potential functional target in Asian gastric cancer. Further, we experimentally demonstrated the translational relevance of this gene as a potential therapeutic target for early-stage gastric cancer in Asian patients. Together, our findings not only provide a valuable information resource for identifying and elucidating the molecular mechanisms of Asian gastric cancer, but also represent a general integrative framework to develop more effective therapeutic targets.