MicroRNA expression, survival, and response to interferon in liver cancer.
MicroRNA expression, survival, and response to interferon in liver cancer.
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DOI：
10.1056/nejmoa0901282
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发表时间：
2009-10-08
期刊：
影响因子：
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通讯作者：
Wang XW
中科院分区：
文献类型：
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作者：
Ji J;Shi J;Budhu A;Yu Z;Forgues M;Roessler S;Ambs S;Chen Y;Meltzer PS;Croce CM;Qin LX;Man K;Lo CM;Lee J;Ng IO;Fan J;Tang ZY;Sun HC;Wang XW
肝细胞癌是一种常见的侵袭性癌症，主要发生在男性。我们研究了患有这种疾病的男性和女性的microRNA表达模式、存活率和对α干扰素的反应。我们分析了三个独立的队列，包括1999年至2003年间接受根治性肿瘤切除的总共455名肝细胞癌患者。对241例肝细胞癌患者进行了microRNA表达谱分析，以确定与肿瘤相关的microRNAs，并确定它们与男性和女性生存的关系。此外，为了验证我们的发现，我们使用定量reverse-transcriptase–polymerase-chain-reaction分析来测量来自两个独立的、前瞻性的、随机的、对照的辅助性干扰素治疗试验的214名患者的microRNA，并评估它们与生存和干扰素治疗反应的关系。在肝细胞癌患者中，女性非肿瘤肝组织miR-26a和miR-26b的表达高于男性。与配对的非癌组织相比，肿瘤组织中miR-26的表达水平降低，这表明miR-26的表达水平也与肝细胞癌有关。此外，miR-26表达降低的肿瘤具有明显的转录模式，基因网络分析表明，核因子κB和白细胞介素6之间的信号通路激活可能在肿瘤的发生发展中发挥作用。MiR-26低表达的肿瘤患者总体生存期较短，但对干扰素治疗的反应好于microRNA高表达的肿瘤患者。男性和女性肝细胞癌患者肝组织中microRNAs的表达模式不同。这些患者的miR-26表达状态与患者的存活率和对干扰素α辅助治疗的反应有关。
Hepatocellular carcinoma is a common and aggressive cancer that occurs mainly in men. We examined microRNA expression patterns, survival, and response to interferon alfa in both men and women with the disease. We analyzed three independent cohorts that included a total of 455 patients with hepatocellular carcinoma who had undergone radical tumor resection between 1999 and 2003. MicroRNA-expression profiling was performed in a cohort of 241 patients with hepatocellular carcinoma to identify tumor-related microRNAs and determine their association with survival in men and women. In addition, to validate our findings, we used quantitative reverse-transcriptase–polymerase-chain-reaction assays to measure microRNAs and assess their association with survival and response to therapy with interferon alfa in 214 patients from two independent, prospective, randomized, controlled trials of adjuvant interferon therapy. In patients with hepatocellular carcinoma, the expression of miR-26a and miR-26b in nontumor liver tissue was higher in women than in men. Tumors had reduced levels of miR-26 expression, as compared with paired noncancerous tissues, which indicated that the level of miR-26 expression was also associated with hepatocellular carcinoma. Moreover, tumors with reduced miR-26 expression had a distinct transcriptomic pattern, and analyses of gene networks revealed that activation of signaling pathways between nuclear factor κB and interleukin-6 might play a role in tumor development. Patients whose tumors had low miR-26 expression had shorter overall survival but a better response to interferon therapy than did patients whose tumors had high expression of the microRNA. The expression patterns of microRNAs in liver tissue differ between men and women with hepatocellular carcinoma. The miR-26 expression status of such patients is associated with survival and response to adjuvant therapy with interferon alfa.