IL-10 and integrin signaling pathways are associated with head and neck cancer progression.
IL-10 and integrin signaling pathways are associated with head and neck cancer progression.
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DOI：
10.1186/s12864-015-2359-6
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发表时间：
2016-01-08
期刊：
影响因子：
4.4
通讯作者：
McWeeney S
中科院分区：
文献类型：
--
作者：
Bornstein S;Schmidt M;Choonoo G;Levin T;Gray J;Thomas CR Jr;Wong M;McWeeney S
头颈部癌症是一种病态，预后不良，在过去的几十年里没有显着改善。本研究的目的是确定进展性头颈癌的生物学途径，为预后和辅助策略提供信息。我们在癌症基因组图谱（TCGA）中确定了235名头颈癌患者，这些患者具有关于治疗性治疗和疾病进展的充分临床注释，以确定进展者和非进展者。我们比较了这两组之间的原发肿瘤基因表达和突变状态。105个基因在进展者和非进展者之间差异表达（FDR < 0.05）。通路分析揭示了与整联蛋白信号传导以及IL-10信号传导相关的多个通路的失调（FDR < 0.05）。许多基因在进展者队列中发生独特突变，包括CTCF中截短突变频率增加（P = 0.007）。鉴定了来源于独特突变和差异表达的组合的11个基因签名（PAGE 4、SMTNL 1、VTN、CA 5A、C1 orf 43、KRTAP 19 -1、LEP、HRH 4、PAGE 5、SEZ 6L、CREB 3）。该特征与总生存率降低相关（对数秩检验; P = 0.03443）。关键临床特征和特征的考克斯模型具有显著性（P = 0.032），在基于淋巴结囊外扩散和单独饮酒的模型中观察到最大的预后改善（P = 0.004）。对尽管治疗仍进展的头颈癌肿瘤进行分子分析，确定IL-10和整合素途径与癌症进展密切相关。此外，我们确定了一个11个基因的签名与患者的诊断。突变分析强调了CTCF在头颈癌进展中的潜在作用，CTCF是长距离染色质相互作用的关键调节因子。本文的在线版本（doi：10.1186/s12864-015-2359-6）包含补充材料，可供授权用户使用。
Head and neck cancer is morbid with a poor prognosis that has not significantly improved in the past several decades. The purpose of this study was to identify biological pathways underlying progressive head and neck cancer to inform prognostic and adjuvant strategies. We identified 235 head and neck cancer patients in The Cancer Genome Atlas (TCGA) with sufficient clinical annotation regarding therapeutic treatment and disease progression to identify progressors and non-progressors. We compared primary tumor gene expression and mutational status between these two groups. 105 genes were differentially expressed between progressors and nonprogressors (FDR < 0.05). Pathway analyses revealed deregulation (FDR < 0.05) of multiple pathways related to integrin signaling as well as IL-10 signaling. A number of genes were uniquely mutated in the progressor cohort including increased frequency of truncating mutations in CTCF (P = 0.007). An 11-gene signature derived from a combination of unique mutations and differential expression was identified (PAGE4, SMTNL1, VTN, CA5A, C1orf43, KRTAP19-1, LEP, HRH4, PAGE5, SEZ6L, CREB3). This signature was associated with decreased overall survival (Logrank Test; P = 0.03443). Cox modeling of both key clinical features and the signature was significant (P = 0.032) with the greatest prognostic improvement seen in the model based on nodal extracapsular spread and alcohol use alone (P = 0.004). Molecular analyses of head and neck cancer tumors that progressed despite treatment, identified IL-10 and integrin pathways to be strongly associated with cancer progression. In addition, we identified an 11-gene signature with implications for patient prognostication. Mutational analysis highlighted a potential role for CTCF, a crucial regulator of long-range chromatin interactions, in head and neck cancer progression. The online version of this article (doi:10.1186/s12864-015-2359-6) contains supplementary material, which is available to authorized users.