A Transcription Factor Signature Can Identify the CMS4 Subtype and Stratify the Prognostic Risk of Colorectal Cancer.
A Transcription Factor Signature Can Identify the CMS4 Subtype and Stratify the Prognostic Risk of Colorectal Cancer.
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DOI：
10.3389/fonc.2022.902974
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发表时间：
2022
影响因子：
4.7
通讯作者：
Wang, Wei
中科院分区：
文献类型：
--
作者：
Zhong, Min-Er;Huang, Ze-Ping;Wang, Xun;Cai, Du;Li, Cheng-Hang;Gao, Feng;Wu, Xiao-Jian;Wang, Wei
结直肠癌（CRC）是一种异质性疾病，目前的分类系统不足以对具有不同风险的患者进行分层。本研究的目的是开发一个通用的，个性化的预后共识分子亚型（CMS）的转录因子（TF）为基础的签名，可以预测CRC的预后。我们从癌症基因组图谱（TCGA）数据库中获得CMS 4和其他CMS亚型CRC之间差异表达的TF标签和靶基因。进行多维网络推理综合分析以识别主基因并建立基于CMS 4-TF的签名。为了验证，应用了内部临床队列（n = 351）和另一个独立的公共CRC队列（n = 565）。通过基因集富集分析（GSEA）和免疫细胞浸润预测来解释模型的生物学意义。开发了称为TF-9的基于CMS 4-TF的标签，其包括九个TF主基因。TF-9高风险组的患者生存率显著更差，无论其临床特征如何。与报告的所有其他特征（0.51 - 0.57）相比，TF-9达到了最高的平均C指数（0.65）。免疫浸润显示，高风险组的微环境受到高度免疫抑制，如TIM 3，CD 39和CD 40的过表达所证明的，这表明高风险患者可能无法直接受益于免疫检查点抑制剂。TF-9特征允许对具有相关临床和生物学意义的患者进行更精确的分类，这可能是改善CRC患者治疗干预的有价值的工具。
Colorectal cancer (CRC) is a heterogeneous disease, and current classification systems are insufficient for stratifying patients with different risks. This study aims to develop a generalized, individualized prognostic consensus molecular subtype (CMS)-transcription factors (TFs)-based signature that can predict the prognosis of CRC. We obtained differentially expressed TF signature and target genes between the CMS4 and other CMS subtypes of CRC from The Cancer Genome Atlas (TCGA) database. A multi-dimensional network inference integrative analysis was conducted to identify the master genes and establish a CMS4-TFs-based signature. For validation, an in-house clinical cohort (n = 351) and another independent public CRC cohort (n = 565) were applied. Gene set enrichment analysis (GSEA) and prediction of immune cell infiltration were performed to interpret the biological significance of the model. A CMS4-TFs-based signature termed TF-9 that includes nine TF master genes was developed. Patients in the TF-9 high-risk group have significantly worse survival, regardless of clinical characteristics. The TF-9 achieved the highest mean C-index (0.65) compared to all other signatures reported (0.51 to 0.57). Immune infiltration revealed that the microenvironment in the high-risk group was highly immune suppressed, as evidenced by the overexpression of TIM3, CD39, and CD40, suggesting that high-risk patients may not directly benefit from the immune checkpoint inhibitors. The TF-9 signature allows a more precise categorization of patients with relevant clinical and biological implications, which may be a valuable tool for improving the tailoring of therapeutic interventions in CRC patients.
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影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H
影响因子：
50.3
作者：
Jackstadt, Rene;van Hooff, Sander R.;Sansom, Owen J.
通讯作者：
Sansom, Owen J.
影响因子：
4.2
作者：
Jiang, Xun;Shen, Tong-Yi;Wang, Feng
通讯作者：
Wang, Feng
MEIS3的抑制作用通过C-MET和AKT产生西妥昔单抗的抗性。
影响因子：
--
作者：
Cai P;Xie Y;Dong M;Zhu Q
通讯作者：
Zhu Q
DOI：
10.1038/s41568-019-0196-7
发表时间：
2019-11
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Bushweller JH
通讯作者：
Bushweller JH