Genomic Alteration Characterization in Colorectal Cancer Identifies a Prognostic and Metastasis Biomarker: FAM83A|IDO1.
Genomic Alteration Characterization in Colorectal Cancer Identifies a Prognostic and Metastasis Biomarker: FAM83A|IDO1.
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DOI：
10.3389/fonc.2021.632430
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发表时间：
2021
影响因子：
4.7
通讯作者：
Han X
中科院分区：
文献类型：
--
作者：
Liu Z;Zhang Y;Dang Q;Wu K;Jiao D;Li Z;Sun Z;Han X
基因组改变构成结直肠癌（CRC）的关键要素。然而，缺乏从全球角度对CRC基因组改变的全面了解。在这项研究中，共招募了15个公共数据集中的2，778名患者。同时收集了30例患者的组织和临床资料。我们成功地确定了两个不同的突变特征集群（MSC）的特点是大量的突变和显性体细胞拷贝数改变（SCNA），分别。MSC-1与DNA错配修复缺陷相关，表现出更频繁的突变，如ATM、BRAF和SMAD 4。BRAF-HMCN和DNAH 17-MDN 1的突变共发生以及MLH-1的甲基化沉默事件仅在MSC-1中发现。MSC-2与年龄和烟草咀嚼习惯的致癌过程相关，表现出显性SCNA，如MYC（8q24.21）和PTEN（10q23.31）缺失以及CCND 3（6p21.1）和ERBB 2（17 q12）扩增。MSC-1具有较高的免疫原性和免疫浸润能力。MSC-2预后较好，间质活化明显。基于这两种亚型，我们在15个独立队列和来自30个样本的qRT-PCR数据中鉴定并验证了FAM 83 A和IDO 1的表达关系作为CRC预后和远处转移的稳健生物标志物。这些结果推进了CRC的精确治疗和临床管理。
Genomic alterations constitute crucial elements of colorectal cancer (CRC). However, a comprehensive understanding of CRC genomic alterations from a global perspective is lacking. In this study, a total of 2,778 patients in 15 public datasets were enrolled. Tissues and clinical information of 30 patients were also collected. We successfully identified two distinct mutation signature clusters (MSC) featured by massive mutations and dominant somatic copy number alterations (SCNA), respectively. MSC-1 was associated with defective DNA mismatch repair, exhibiting more frequent mutations such as ATM, BRAF, and SMAD4. The mutational co-occurrences of BRAF-HMCN and DNAH17-MDN1 as well as the methylation silence event of MLH-1 were only found in MSC-1. MSC-2 was linked to the carcinogenic process of age and tobacco chewing habit, exhibiting dominant SCNA such as MYC (8q24.21) and PTEN (10q23.31) deletion as well as CCND3 (6p21.1) and ERBB2 (17q12) amplification. MSC-1 displayed higher immunogenicity and immune infiltration. MSC-2 had better prognosis and significant stromal activation. Based on the two subtypes, we identified and validated the expression relationship of FAM83A and IDO1 as a robust biomarker for prognosis and distant metastasis of CRC in 15 independent cohorts and qRT-PCR data from 30 samples. These results advance precise treatment and clinical management in CRC.
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影响因子：
12.4
作者：
Linnekamp, Janneke F.;van Hooff, Sander R.;Medema, Jan Paul
通讯作者：
Medema, Jan Paul
影响因子：
3.4
作者：
Casado-Saenz, E.;Feliu, J.;Garcia-Carbonero, R.
通讯作者：
Garcia-Carbonero, R.
影响因子：
3.7
作者：
Kiely M;Tse LA;Koka H;Wang D;Lee P;Wang F;Wu C;Tsang KH;Chan WC;Law SH;Zhang H;Karlins E;Zhu B;Hutchinson A;Hicks B;Zhu B;Yang XR
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Yang XR
影响因子：
2.1
作者：
Manic G;Obrist F;Sistigu A;Vitale I
通讯作者：
Vitale I
影响因子：
45.3
作者：
Douillard, Jean-Yves;Siena, Salvatore;Gansert, Jennifer
通讯作者：
Gansert, Jennifer