Underexpression of Specific Interferon Genes Is Associated with Poor Prognosis of Melanoma.
Underexpression of Specific Interferon Genes Is Associated with Poor Prognosis of Melanoma.
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特异性干扰素基因的不足与黑色素瘤的预后不良有关。
DOI：
10.1371/journal.pone.0170025
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Zare H
中科院分区：
文献类型：
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作者：
Zainulabadeen A;Yao P;Zare H
由于黑色素瘤的预后是具有挑战性的和不准确的，当使用当前的临床方法，临床医生正在寻求更准确的分子标记物，以改善风险模型。因此，我们对来自癌症基因组图谱（TCGA）皮肤黑色素瘤队列的404个样本进行了生存分析。使用我们最近开发的基因网络模型，我们确定了可以自信地预测黑色素瘤预后的生物学特征（p值< 10 - 5）。我们的模型预测38例为低风险，54例为高风险。低风险病例生存至少5年的概率为64%，高风险病例为14%。特别是，我们发现有丝分裂细胞周期途径中特定基因的过表达和干扰素途径中特定基因的低表达都与不良预后相关。我们表明，我们的预测模型比传统的克拉克分期方法更准确地评估风险。因此，我们的模型可以帮助临床医生更有效地设计治疗策略。此外，我们的发现揭示了黑色素瘤的生物学及其预后。这是第一个在体内研究，表明干扰素途径和黑色素瘤的预后之间的关联。
Because the prognosis of melanoma is challenging and inaccurate when using current clinical approaches, clinicians are seeking more accurate molecular markers to improve risk models. Accordingly, we performed a survival analysis on 404 samples from The Cancer Genome Atlas (TCGA) cohort of skin cutaneous melanoma. Using our recently developed gene network model, we identified biological signatures that confidently predict the prognosis of melanoma (p-value < 10−5). Our model predicted 38 cases as low–risk and 54 cases as high–risk. The probability of surviving at least 5 years was 64% for low–risk and 14% for high–risk cases. In particular, we found that the overexpression of specific genes in the mitotic cell cycle pathway and the underexpression of specific genes in the interferon pathway are both associated with poor prognosis. We show that our predictive model assesses the risk more accurately than the traditional Clark staging method. Therefore, our model can help clinicians design treatment strategies more effectively. Furthermore, our findings shed light on the biology of melanoma and its prognosis. This is the first in vivo study that demonstrates the association between the interferon pathway and the prognosis of melanoma.