Proteomic Analyses Identify Therapeutic Targets in Hepatocellular Carcinoma.
Proteomic Analyses Identify Therapeutic Targets in Hepatocellular Carcinoma.
复制标题
DOI：
10.3389/fonc.2022.814120
复制
发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
肝细胞癌是全球第四大癌症相关死亡原因。虽然已经开发了许多靶向治疗方法，但大多数肝细胞癌肿瘤没有临床上可操作的突变。蛋白质水平的异常，特别是那些在基因组水平上不明显的异常，提供了治疗的机会，但很少被系统地描述在肝细胞癌中。在这项研究中，我们使用全球质谱学(MS)蛋白质组学数据对来自两个与乙肝相关的肝癌患者队列的260个原发肿瘤进行了蛋白质基因组学分析。结合肿瘤正常和肿瘤间的分析，我们确定了肝癌中高表达的靶点，包括PDGFRb、FGFR4、ERBB2/3、CDK6激酶和MFAP5、HMCN1和HSP蛋白，其中许多蛋白显示出低频率的基因组和/或转录异常。FGFR4和HSP蛋白的表达与对相应抑制剂的反应显著相关。我们的结果提供了肝细胞癌中蛋白质靶点的目录，并证明了蛋白质组学方法在缺乏可药物突变的癌症类型中推进精确医学的潜力。
Hepatocellular carcinoma (HCC) is the fourth cause of cancer-related mortality worldwide. While many targeted therapies have been developed, the majority of HCC tumors do not harbor clinically actionable mutations. Protein-level aberrations, especially those not evident at the genomic level, present therapeutic opportunities but have rarely been systematically characterized in HCC. In this study, we performed proteogenomic analyses of 260 primary tumors from two HBV-related HCC patient cohorts with global mass-spectrometry (MS) proteomics data. Combining tumor-normal and inter-tumor analyses, we identified overexpressed targets including PDGFRB, FGFR4, ERBB2/3, CDK6 kinases and MFAP5, HMCN1, and Hsp proteins in HCC, many of which showed low frequencies of genomic and/or transcriptomic aberrations. Protein expression of FGFR4 kinase and Hsp proteins were significantly associated with response to their corresponding inhibitors. Our results provide a catalog of protein targets in HCC and demonstrate the potential of proteomics approaches in advancing precision medicine in cancer types lacking druggable mutations.
登录
查看更多内容
影响因子：
16.6
作者：
Huang KL;Li S;Mertins P;Cao S;Gunawardena HP;Ruggles KV;Mani DR;Clauser KR;Tanioka M;Usary J;Kavuri SM;Xie L;Yoon C;Qiao JW;Wrobel J;Wyczalkowski MA;Erdmann-Gilmore P;Snider JE;Hoog J;Singh P;Niu B;Guo Z;Sun SQ;Sanati S;Kawaler E;Wang X;Scott A;Ye K;McLellan MD;Wendl MC;Malovannaya A;Held JM;Gillette MA;Fenyö D;Kinsinger CR;Mesri M;Rodriguez H;Davies SR;Perou CM;Ma C;Reid Townsend R;Chen X;Carr SA;Ellis MJ;Ding L
通讯作者：
Ding L
影响因子：
16.6
作者：
Huang KL;Scott AD;Zhou DC;Wang LB;Weerasinghe A;Elmas A;Liu R;Wu Y;Wendl MC;Wyczalkowski MA;Baral J;Sengupta S;Lai CW;Ruggles K;Payne SH;Raphael B;Fenyö D;Chen K;Mills G;Ding L
通讯作者：
Ding L
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
7
作者：
Huang, Kuan-lin;Wu, Yige;Ding, Li
通讯作者：
Ding, Li
影响因子：
158.5
作者：
Finn, Richard S.;Qin, Shukui;Cheng, Ann-Lii
通讯作者：
Cheng, Ann-Lii