DNA Damage Repair Profiles Alteration Characterize a Hepatocellular Carcinoma Subtype With Unique Molecular and Clinicopathologic Features.
DNA Damage Repair Profiles Alteration Characterize a Hepatocellular Carcinoma Subtype With Unique Molecular and Clinicopathologic Features.
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DNA 损伤修复谱的改变表征了具有独特分子和临床病理学特征的肝细胞癌亚型
DOI：
10.3389/fimmu.2021.715460
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发表时间：
2021
影响因子：
7.3
通讯作者：
Yang H
中科院分区：
文献类型：
--
作者：
Lin P;Gao RZ;Wen R;He Y;Yang H
肝细胞癌（HCC）是最常见的恶性肿瘤之一，其分子表型具有高度异质性。我们通过整合多组学数据研究了HCC中DNA损伤修复（DDR）的改变。肝癌患者被分为两种具有不同临床和分子特征的异质亚型：DDR激活亚型和DDR抑制亚型。DDR激活亚组的特征在于较差的预后和临床病理特征，导致侵袭性临床行为。DDR抑制类肿瘤具有独特的临床和分子特征，往往具有上级存活率。最终生成DDR亚型签名以实现HCC DDR分类，并且通过使用多层数据队列来确认结果。此外，两种DDR亚型之间的免疫特征和免疫治疗应答也不同。总之，这项研究说明了肝癌的DDR异质性，有助于理解负责独特的肿瘤DDR配置文件的个性化临床病理和分子机制。
Hepatocellular carcinoma (HCC) is one of the most common malignancies and displays high heterogeneity of molecular phenotypes. We investigated DNA damage repair (DDR) alterations in HCC by integrating multi-omics data. HCC patients were classified into two heterogeneous subtypes with distinct clinical and molecular features: the DDR-activated subtype and the DDR-suppressed subtype. The DDR-activated subgroup is characterized by inferior prognosis and clinicopathological features that result in aggressive clinical behavior. Tumors of the DDR-suppressed class, which have distinct clinical and molecular characteristics, tend to have superior survival. A DDR subtype signature was ultimately generated to enable HCC DDR classification, and the results were confirmed by using multi-layer date cohorts. Furthermore, immune profiles and immunotherapy responses are also different between the two DDR subtypes. Altogether, this study illustrates the DDR heterogeneity of HCCs and is helpful to the understanding of personalized clinicopathological and molecular mechanisms responsible for unique tumor DDR profiles.
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影响因子：
64.5
作者：
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu;Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
CancerSubtypes：用于分子癌症亚型识别、验证和可视化的 R/Bioconductor 软件包
影响因子：
5.8
作者：
Xu, Taosheng;Thuc Duy Le;Li, Jiuyong
通讯作者：
Li, Jiuyong
影响因子：
7
作者：
Melssen M;Slingluff CL Jr
通讯作者：
Slingluff CL Jr
影响因子：
64.8
作者：
Mariathasan S;Turley SJ;Nickles D;Castiglioni A;Yuen K;Wang Y;Kadel EE III;Koeppen H;Astarita JL;Cubas R;Jhunjhunwala S;Banchereau R;Yang Y;Guan Y;Chalouni C;Ziai J;Şenbabaoğlu Y;Santoro S;Sheinson D;Hung J;Giltnane JM;Pierce AA;Mesh K;Lianoglou S;Riegler J;Carano RAD;Eriksson P;Höglund M;Somarriba L;Halligan DL;van der Heijden MS;Loriot Y;Rosenberg JE;Fong L;Mellman I;Chen DS;Green M;Derleth C;Fine GD;Hegde PS;Bourgon R;Powles T
通讯作者：
Powles T
影响因子：
11.2
作者：
Roessler S;Jia HL;Budhu A;Forgues M;Ye QH;Lee JS;Thorgeirsson SS;Sun Z;Tang ZY;Qin LX;Wang XW
通讯作者：
Wang XW