A Dynamic Transcription Factor Signature Along the Colorectal Adenoma-Carcinoma Sequence in Patients With Co-Occurrent Adenoma and Carcinoma.
A Dynamic Transcription Factor Signature Along the Colorectal Adenoma-Carcinoma Sequence in Patients With Co-Occurrent Adenoma and Carcinoma.
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DOI：
10.3389/fonc.2021.597447
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发表时间：
2021
影响因子：
4.7
通讯作者：
Huang P
中科院分区：
文献类型：
--
作者：
Pan Z;He Y;Zhu W;Xu T;Hu X;Huang P
结直肠癌(CRC)通常发生于良性腺瘤，在基因改变的逐步积累后发生。在这里，我们描绘了转录因子(TF)在粘膜-腺瘤-癌进展序列中的动态景观。从GSE117606获得了腺瘤、癌和正常粘膜的转录组数据。在R软件中进行差异表达因子(DE-TF)的鉴定和后续的功能注释。用Short-Time-Series Expression Miner软件对DE-TF的表达模式进行聚类分析。然后，采用模块化共表达分析、Kaplan-Meier生存分析、突变谱分析和基因集浓缩分析来研究TF在结直肠肿瘤发生中的动态变化。最后，应用组织芯片，包括51个肿瘤、32个腺瘤和53个正常组织，通过免疫组织化学染色来检测有意义的候选基因的表达。与正常组织相比，发现了20个(腺瘤样本)和29个(肿瘤样本)DE-TF。在整个病程中，DE-TF的28个表达模式和4个共表达模块被聚为一类。值得注意的是，6个DE-TF，DACH1，GTF2IRD1，MEIS2，NR3C2，SOX9和SPIB，被鉴定为沿着结直肠腺瘤-癌序列具有动态特征。动态特征对GO的富集、预后和共表达分析具有重要意义。在6-TF信号中，GTF2IRD1、SPIB和NR3C2在结直肠癌进展中的作用尚不清楚。免疫组织化学证实GTF2IRD1在黏膜-腺瘤-癌序列中显著增强，而SPIB和NR3C2在病程中间质中持续下降。我们的研究提供了一个动态的6-TF信号贯穿于大肠粘膜-腺瘤-癌的整个过程。这些发现加深了对结直肠癌发病机制的认识。
Colorectal carcinoma (CRC) often arises from benign adenoma after a stepwise accumulation of genetic alterations. Here, we profiled the dynamic landscapes of transcription factors (TFs) in the mucosa-adenoma-carcinoma progression sequence. The transcriptome data of co-occurrent adenoma, carcinoma, and normal mucosa samples were obtained from GSE117606. Identification of differentially expressed TFs (DE-TFs) and subsequent function annotation were conducted in R software. Expression patterns of DE-TFs were clustered by Short Time-series Expression Miner software. Thereafter, modular co-expression analysis, Kaplan-Meier survival analysis, mutation profiling, and gene set enrichment analysis were conducted to investigate TF dynamics in colorectal tumorigenesis. Finally, tissue microarrays, including 51 tumors, 32 adenomas, and 53 normal tissues, were employed to examine the expression of significant candidates by immunohistochemistry staining. Compared to normal tissues, 20 (in adenoma samples) and 29 (in tumor samples) DE-TFs were identified. During the disease course, 28 expression patterns for DE-TFs and four co-expression modules were clustered. Notably, six DE-TFs, DACH1, GTF2IRD1, MEIS2, NR3C2, SOX9, and SPIB, were identified as having a dynamic signature along the colorectal adenoma-carcinoma sequence. The dynamic signature was of significance in GO enrichment, prognosis, and co-expression analysis. Among the 6-TF signature, the roles of GTF2IRD1, SPIB and NR3C2 in CRC progression are unclear. Immunohistochemistry validation showed that GTF2IRD1 enhanced significantly throughout the mucosa-adenoma-carcinoma sequence, while SPIB and NR3C2 kept decreasing in stroma during the disease course. Our study provided a dynamic 6-TF signature throughout the course of colorectal mucosa-adenoma-carcinoma. These findings deepened the understanding of colorectal cancer pathogenesis.
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影响因子：
--
作者：
Ashkenazi S;Ortenberg R;Besser M;Schachter J;Markel G
通讯作者：
Markel G
DOI：
10.3390/molecules23061479
发表时间：
2018-06-19
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Lambert M;Jambon S;Depauw S;David-Cordonnier MH
通讯作者：
David-Cordonnier MH
影响因子：
7.5
作者：
Murakami, Takashi;Mitomi, Hiroyuki;Watanabe, Sumio
通讯作者：
Watanabe, Sumio
影响因子：
5.3
作者：
Wiederschain, Dmitri;Chen, Lin;Benson, John D.
通讯作者：
Benson, John D.
影响因子：
9.8
作者：
Chang HY;Sneddon JB;Alizadeh AA;Sood R;West RB;Montgomery K;Chi JT;van de Rijn M;Botstein D;Brown PO
通讯作者：
Brown PO