Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Front Immunol. 2021 Aug 12;12:715460. doi: 10.3389/fimmu.2021.715460. eCollection 2021.
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.
肝细胞癌（HCC）是最常见的恶性肿瘤之一，表现出分子表型的高度异质性。我们通过整合多组学数据研究了 HCC 中的 DNA 损伤修复（DDR）改变。通过整合多组学数据，我们将 HCC 患者分为具有不同临床和分子特征的两个异质亚型：DDR 激活亚型和 DDR 抑制亚型。DDR 激活亚组的预后较差，且具有导致侵袭性临床行为的临床病理特征。具有独特临床和分子特征的 DDR 抑制类肿瘤的生存情况较好。最终生成了一个 DDR 亚型特征，以实现 HCC DDR 分类，并通过使用多层数据队列进行了验证。此外，两种 DDR 亚型之间的免疫特征和免疫治疗反应也不同。总之，本研究说明了 HCC 的 DDR 异质性，有助于理解导致独特肿瘤 DDR 谱的个性化临床病理和分子机制。
