Identification of Mutation Landscape and Immune Cell Component for Liver Hepatocellular Carcinoma Highlights Potential Therapeutic Targets and Prognostic Markers.
Identification of Mutation Landscape and Immune Cell Component for Liver Hepatocellular Carcinoma Highlights Potential Therapeutic Targets and Prognostic Markers.
复制标题
肝癌突变景观和免疫细胞成分的鉴定突出了潜在的治疗靶点和预后标志物
DOI：
10.3389/fgene.2021.737965
复制
发表时间：
2021
影响因子：
3.7
通讯作者：
Han P
中科院分区：
文献类型：
--
作者：
Wang H;Jiang W;Wang H;Wei Z;Li H;Yan H;Han P
肝细胞癌(LIHC)是一种原发恶性肿瘤，对晚期患者缺乏有效的治疗方法。虽然有许多研究揭示了LIHC的致癌机制，但很少有研究整合多组学数据来系统分析发病机制和揭示潜在的治疗靶点。在这里，我们整合了基因组变异数据和通过高通量测序获得的RNA-seq图谱，以定义高基因组不稳定性和低基因组不稳定性样本。报告了突变情况，晚期LIHC患者的特征是基因组高度不稳定。我们发现，为了满足肿瘤的增殖和侵袭，肿瘤微环境在突变的驱动下进行了代谢重编。此外，共表达网络确定了三个突变的长非编码RNA作为潜在的治疗靶点，它们可以通过参与特定的致癌机制来促进肿瘤的进展。通过检测RP11-502I4.3、SPINK5、CHRM3、SLC5A12和RP11-467L13.7基因与患者生存的关系，确定了5个潜在的预后标记。通过对LIHC免疫格局的描述，发现免疫原性的丧失是免疫检查点抑制的关键因素。巨噬细胞被发现与患者风险评分显著相关，高水平的巨噬细胞加速了患者的死亡。综上所述，本研究揭示的LIHC突变驱动机制和免疫格局将为精准医学服务。
Liver hepatocellular carcinoma (LIHC) is a primary malignancy, and there is a lack of effective treatment for advanced patients. Although numerous studies exist to reveal the carcinogenic mechanism of LIHC, few studies have integrated multi-omics data to systematically analyze pathogenesis and reveal potential therapeutic targets. Here, we integrated genomic variation data and RNA-seq profiles obtained by high-throughput sequencing to define high- and low-genomic instability samples. The mutational landscape was reported, and the advanced patients of LIHC were characterized by high-genomic instability. We found that the tumor microenvironment underwent metabolic reprograming driven by mutations accumulate to satisfy tumor proliferation and invasion. Further, the co-expression network identifies three mutant long non-coding RNAs as potential therapeutic targets, which can promote tumor progression by participating in specific carcinogenic mechanisms. Then, five potential prognostic markers (RP11-502I4.3, SPINK5, CHRM3, SLC5A12, and RP11-467L13.7) were identified by examining the association of genes and patient survival. By characterizing the immune landscape of LIHC, loss of immunogenicity was revealed as a key factor of immune checkpoint suppression. Macrophages were found to be significantly associated with patient risk scores, and high levels of macrophages accelerated patient mortality. In summary, the mutation-driven mechanism and immune landscape of LIHC revealed by this study will serve precision medicine.
登录
查看更多内容
影响因子：
16.6
作者：
Chatsirisupachai K;Lesluyes T;Paraoan L;Van Loo P;de Magalhães JP
通讯作者：
de Magalhães JP
影响因子：
81.5
作者：
Llovet, Josep M.;Zucman-Rossi, Jessica;Gores, Gregory
通讯作者：
Gores, Gregory
单细胞 RNA 测序强调了炎性癌症相关成纤维细胞在膀胱尿路上皮癌中的作用。
影响因子：
16.6
作者：
Chen Z;Zhou L;Liu L;Hou Y;Xiong M;Yang Y;Hu J;Chen K
通讯作者：
Chen K
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
影响因子：
4
作者：
Li SQ;Jiang YH;Lin J;Zhang J;Sun F;Gao QF;Zhang L;Chen QG;Wang XZ;Ying HQ
通讯作者：
Ying HQ