A gene expression and pre-mRNA splicing signature that marks the adenoma-adenocarcinoma progression in colorectal cancer.
A gene expression and pre-mRNA splicing signature that marks the adenoma-adenocarcinoma progression in colorectal cancer.
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DOI：
10.1371/journal.pone.0087761
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Corcos L
中科院分区：
文献类型：
--
作者：
Pesson M;Volant A;Uguen A;Trillet K;De La Grange P;Aubry M;Daoulas M;Robaszkiewicz M;Le Gac G;Morel A;Simon B;Corcos L
大多数结直肠癌（CRC）起源于结直肠腺瘤（CRA），但从结直肠正常粘膜到腺瘤，然后到腺癌的进展的转录组学数据很少。这些过渡步骤进行了研究，使用微阵列，无论是在基因表达水平和选择性前mRNA剪接。与正常粘膜相比，CRA中许多基因和外显子的表达异常，甚至高于CRC。已知的CRC相关生物学通路在CRA中发生了改变，但也发现了几种新的富集通路，如补体和凝血级联。我们还确定了四个交叉转录签名，可以区分CRA正常粘膜或CRC，包括CRA和CRC样本中差异失调的40个基因的签名。这些基因中的大多数在不同的癌症中被描述，包括FBLN1或INHBA，但在CRC中只有少数。在蛋白质水平上也观察到了其中几种变化。此外，这些基因中的20%（即CFH、CD4AB、DPT、FBLN1、ITIH5、NR3C2、SLIT 3和TIMP 1）在CRA中显示出改变的前mRNA剪接。作为自CRA阶段以来发生并在CRC中维持的全局变异，这40个基因集的表达和剪接变化可以从CRA活检分析中标记癌症发生的风险。
It is widely accepted that most colorectal cancers (CRCs) arise from colorectal adenomas (CRAs), but transcriptomic data characterizing the progression from colorectal normal mucosa to adenoma, and then to adenocarcinoma are scarce. These transition steps were investigated using microarrays, both at the level of gene expression and alternative pre-mRNA splicing. Many genes and exons were abnormally expressed in CRAs, even more than in CRCs, as compared to normal mucosae. Known biological pathways involved in CRC were altered in CRA, but several new enriched pathways were also recognized, such as the complement and coagulation cascades. We also identified four intersectional transcriptional signatures that could distinguish CRAs from normal mucosae or CRCs, including a signature of 40 genes differentially deregulated in both CRA and CRC samples. A majority of these genes had been described in different cancers, including FBLN1 or INHBA, but only a few in CRC. Several of these changes were also observed at the protein level. In addition, 20% of these genes (i.e. CFH, CRYAB, DPT, FBLN1, ITIH5, NR3C2, SLIT3 and TIMP1) showed altered pre-mRNA splicing in CRAs. As a global variation occurring since the CRA stage, and maintained in CRC, the expression and splicing changes of this 40-gene set may mark the risk of cancer occurrence from analysis of CRA biopsies.
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影响因子：
4.8
作者：
Bommer, GT;Jäger, CJ;Kolligs, FT
通讯作者：
Kolligs, FT
影响因子：
24.5
作者：
Citarda, F;Tomaselli, G;Crespi, M
通讯作者：
Crespi, M
影响因子：
15.9
作者：
Huang, Jian;Zheng, Da-Li;Han, Ze-Guang
通讯作者：
Han, Ze-Guang
影响因子：
11.1
作者：
Cattaneo, Elisa;Laczko, Endre;Buffoli, Federico;Zorzi, Fausto;Bianco, Maria Antonia;Menigatti, Mirco;Bartosova, Zdena;Haider, Ritva;Helmchen, Birgit;Sabates-Bellver, Jacob;Tiwari, Amit;Jiricny, Josef;Marra, Giancarlo
通讯作者：
Marra, Giancarlo
DOI：
10.3233/clo-2009-0458
发表时间：
2009
期刊：
Cellular oncology : the official journal of the International Society for Cellular Oncology
影响因子：
--
作者：
Galamb O;Sipos F;Spisák S;Galamb B;Krenács T;Valcz G;Tulassay Z;Molnár B
通讯作者：
Molnár B