H2AFZ Is a Prognostic Biomarker Correlated to TP53 Mutation and Immune Infiltration in Hepatocellular Carcinoma.
H2AFZ Is a Prognostic Biomarker Correlated to TP53 Mutation and Immune Infiltration in Hepatocellular Carcinoma.
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DOI：
10.3389/fonc.2021.701736
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发表时间：
2021
影响因子：
4.7
通讯作者：
Sun D
中科院分区：
文献类型：
--
作者：
Dong M;Chen J;Deng Y;Zhang D;Dong L;Sun D
H2 A家族成员Z（H2 AFZ）是编码H2A.Z.1的高度保守基因，H2A.Z.1是组蛋白变体H2A.Z的同种型，并且与癌症有关。在这项研究中，我们报告H2 AFZ的过度表达与肝癌患者的肿瘤恶性程度和预后不良有关。功能网络分析表明，H2 AFZ主要通过涉及多种癌症相关激酶和转录因子E2 F1的途径调节细胞周期信号传导和DNA复制。进一步的研究表明，H2 AFZ过表达受TP 53突变的调控，并导致HCC细胞快速增殖表型和侵袭行为的减弱。此外，我们发现H2 AFZ与免疫浸润相关，并与免疫检查点基因共表达，包括HCC中的CD 274（PD-L1），CTLA-4，HAVCR 2（TIM 3），LAG 3，PDCD 1（PD-1）和TIGIT（VSIG 9），表明H2 AFZ过表达的HCC患者可能对免疫检查点阻断（ICB）敏感。综合分析表明，H2 AFZhigh/TP 53 mut患者的OS和PFS时间最短，但最有可能对ICB产生应答。这些结果表明，H2 AFZ具有潜在的价值，作为一种新的预后指标肝癌患者，并与免疫浸润在肝癌，奠定了基础，为今后的研究肝癌的调查和干预。
H2A family member Z (H2AFZ) is a highly conserved gene encoding H2A.Z.1, an isoform of histone variant H2A.Z, and is implicated in cancer. In this study, we report that overexpression of H2AFZ is associated with tumor malignancy and poor prognosis in HCC patients. Functional network analysis suggested that H2AFZ mainly regulates cell cycle signaling and DNA replication via pathways involving several cancer-related kinases and transcription factor E2F1. Further studies revealed that H2AFZ overexpression is regulated by TP53 mutation and led to an attenuation of rapid proliferation phenotype and aggressive behavior in HCC cells. Moreover, we found that H2AFZ was related to immune infiltrations and was co-expressed with immune checkpoint genes, including CD274 (PD-L1), CTLA-4, HAVCR2 (TIM3), LAG3, PDCD1 (PD-1), and TIGIT (VSIG9) in HCC, indicating that H2AFZ-overexpressed HCC patients may be sensitive to immune checkpoint blockades (ICBs). Integrated analysis suggested that H2AFZhigh/TP53mut patients had the shortest OS and PFS time, but most likely to respond to ICBs. These findings indicate that the H2AFZ possesses potential value as a novel prognostic indicator for HCC patients and is correlated with immune infiltration in HCC, laying a foundation for future study of HCC investigation and intervention.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
64.5
作者：
Benci JL;Xu B;Qiu Y;Wu TJ;Dada H;Twyman-Saint Victor C;Cucolo L;Lee DSM;Pauken KE;Huang AC;Gangadhar TC;Amaravadi RK;Schuchter LM;Feldman MD;Ishwaran H;Vonderheide RH;Maity A;Wherry EJ;Minn AJ
通讯作者：
Minn AJ
GEPIA：用于癌症和正常基因表达谱和交互式分析的网络服务器。
影响因子：
14.9
作者：
Tang Z;Li C;Kang B;Gao G;Li C;Zhang Z
通讯作者：
Zhang Z
DOI：
10.1038/s41580-020-0262-8
发表时间：
2020-09
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Martire S;Banaszynski LA
通讯作者：
Banaszynski LA
影响因子：
8.8
作者：
Domaschenz, Renae;Kurscheid, Sebastian;Tremethick, David J.
通讯作者：
Tremethick, David J.