Widespread parainflammation in human cancer.
Widespread parainflammation in human cancer.
复制标题
人类癌症中广泛的副炎症。
DOI：
10.1186/s13059-016-0995-z
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发表时间：
2016-07-08
期刊：
影响因子：
12.3
通讯作者：
Ben-Neriah Y
中科院分区：
文献类型：
--
作者：
Aran D;Lasry A;Zinger A;Biton M;Pikarsky E;Hellman A;Butte AJ;Ben-Neriah Y
慢性炎症已被认为是癌症的标志之一。我们最近发现，parainflammation，一个独特的变体之间的炎症稳态和慢性炎症，强烈促进小鼠肠道肿瘤后，p53的损失。在这里，我们探讨人类癌症中副炎症的患病率，并确定其与影响治疗和预后的某些分子和临床参数的关系。我们生成了一个转录组签名，以识别许多原发性人类肿瘤和癌细胞系中的副炎症，与其正常组织对应物和肿瘤微环境不同，并表明副炎症阳性肿瘤富含p53突变，并与预后不良相关。非甾体类抗炎药（NSAID）治疗可抑制小鼠和人类癌症的副炎症，这可能解释了NSAID对癌症的保护作用。我们的结论是，副炎症，一种低度炎症，在人类癌症中广泛流行，特别是在通常含有p53突变的癌症类型中。我们的数据表明，副炎症可能是p53突变的驱动因素，也是NSAID治疗预防癌症的指南。本文的在线版本（doi：10.1186/s13059-016-0995-z）包含补充材料，可供授权用户使用。
Chronic inflammation has been recognized as one of the hallmarks of cancer. We recently showed that parainflammation, a unique variant of inflammation between homeostasis and chronic inflammation, strongly promotes mouse gut tumorigenesis upon p53 loss. Here we explore the prevalence of parainflammation in human cancer and determine its relationship to certain molecular and clinical parameters affecting treatment and prognosis. We generated a transcriptome signature to identify parainflammation in many primary human tumors and carcinoma cell lines as distinct from their normal tissue counterparts and the tumor microenvironment and show that parainflammation-positive tumors are enriched for p53 mutations and associated with poor prognosis. Non-steroidal anti-inflammatory drug (NSAID) treatment suppresses parainflammation in both murine and human cancers, possibly explaining a protective effect of NSAIDs against cancer. We conclude that parainflammation, a low-grade form of inflammation, is widely prevalent in human cancer, particularly in cancer types commonly harboring p53 mutations. Our data suggest that parainflammation may be a driver for p53 mutagenesis and a guide for cancer prevention by NSAID treatment. The online version of this article (doi:10.1186/s13059-016-0995-z) contains supplementary material, which is available to authorized users.