Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies
文献类型：期刊论文
| 作者 | Liu, Qian3,4; Zhang, Jing3; Guo, Chenchen5; Wang, Mengcheng5,6; Wang, Chenfei7,8; Yan, Yilv3; Sun, Liangdong3; Wang, Di3; Zhang, Lele9; Yu, Huansha3 |
| 刊名 | CELL
 |
| 出版日期 | 2024-01-04 |
| 卷号 | 187期号:1页码:49 |
| ISSN号 | 0092-8674 |
| DOI | 10.1016/j.cell.2023.12.004 |
| 通讯作者 | Liu, Qian() ; Gao, Daming(dgao@sibcb.ac.cn) ; Ji, Hongbin(hbji@sibcb.ac.cn) ; Zhou, Hu(zhouhu@simm.ac.cn) ; Zhang, Peng(zhangpeng1121@tongji.edu.cn) |
| 英文摘要 | We performed comprehensive proteogenomic characterization of small cell lung cancer (SCLC) using paired tumors and adjacent lung tissues from 112 treatmentnaive patients who underwent surgical resection. Integrated multi-omics analysis illustrated cancer biology downstream of genetic aberrations and highlighted oncogenic roles of FAT1 mutation, RB1 deletion, and chromosome 5q loss. Two prognostic biomarkers, HMGB3 and CASP10, were identified. Overexpression of HMGB3 promoted SCLC cell migration via transcriptional regulation of cell junction-related genes. Immune landscape characterization revealed an association between ZFHX3 mutation and high immune infiltration and underscored a potential immunosuppressive role of elevated DNA damage response activity via inhibition of the cGAS-STING pathway. Multi-omics clustering identified four subtypes with subtype-specific therapeutic vulnerabilities. Cell line and patient-derived xenograft-based drug tests validated the specific therapeutic responses predicted by multi-omics subtyping. This study provides a valuable resource as well as insights to better understand SCLC biology and improve clinical practice. |
| WOS关键词 | TO-MESENCHYMAL TRANSITION ; DNA-DAMAGE REPAIR ; MOLECULAR SIGNATURES ; GENOMIC ANALYSIS ; READ ALIGNMENT ; POOR-PROGNOSIS ; AURORA KINASE ; MUTATIONS ; GENE ; PROLIFERATION |
| 资助项目 | National Natural Science Foundation of China[82125001] ; National Natural Science Foundation of China[81972172] ; National Natural Science Foundation of China[81925029] ; National Natural Science Foundation of China[82230098] ; National Natural Science Foundation of China[32221002] ; National Natural Science Foundation of China[81790253] ; National Natural Science Foundation of China[81872312] ; National Natural Science Foundation of China[82011540007] ; National Natural Science Foundation of China[31621003] ; National Natural Science Foundation of China[82030083] ; National Key Research and Development Program of China[2022YFA1302902] ; National Key Research and Development Program of China[2020YFA0509001] ; National Key Research and Development Program of China[2020YFA0803203] ; National Key Research and Development Program of China[2019YFA0802102] ; National Key Research and Development Program of China[2022YFA1103900] ; National Key Research and Development Program of China[2020YFA0803300] ; Innovation Program of Shanghai Municipal Edu-cation Commission[2023ZKZD33] ; Foundation of Shanghai Pulmo-nary Hospital[FKCX2304] ; Shanghai Young Excellent Academic Leader Program[20XD1424900] ; Shanghai Municipal Science and Technology Major Project ; CAS project for young scientists in basic research[YSBR-014] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB19020201] ; Basic Frontier Sci-entific Research Program of Chinese Academy of Science[ZDBS-LY-SM006] ; International Cooperation Project of Chinese Academy of Sci-ences[153D31KYSB20190035] ; Innovative Research Team of High-Level Local Universities in Shanghai[SSMU-ZLCX20180500] ; China Postdoctoral Science Foundation[2023M732650] ; China Postdoctoral Science Foundation[2022M713138] ; China Postdoctoral Science Foundation[2022T150646] ; Institutional Technology Service Center of the Shanghai Institute of Materia Medica ; US National Cancer Institute ; CPTAC collaborates with international organizations/institu-tions |
| WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
| 语种 | 英语 |
| 出版者 | CELL PRESS |
| WOS记录号 | WOS:001153127700001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/308954]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Liu, Qian; Gao, Daming; Ji, Hongbin; Zhou, Hu; Zhang, Peng |
| 作者单位 | 1.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 2.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200120, Peoples R China 3.Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Thorac Surg, Shanghai 200433, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Dept Analyt Chem, Shanghai 201203, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol, Shanghai 200031, Peoples R China 6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 7.Tongji Univ, Tongji Hosp, Sch Life Sci & Technol, Dept Orthoped,Key Lab Spine & Spinal Cord Injury R, Shanghai 200092, Peoples R China 8.Tongji Univ, Frontier Sci Ctr Stem Cells, Sch Life Sci & Technol, Shanghai 200092, Peoples R China 9.Tongji Univ, Shanghai Pulm Hosp, Sch Med, Cent Lab, Shanghai 200433, Peoples R China 10.Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Pathol, Shanghai 200433, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Qian,Zhang, Jing,Guo, Chenchen,et al. Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies[J]. CELL,2024,187(1):49. |
| APA | Liu, Qian.,Zhang, Jing.,Guo, Chenchen.,Wang, Mengcheng.,Wang, Chenfei.,...&Zhang, Peng.(2024).Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies.CELL,187(1),49. |
| MLA | Liu, Qian,et al."Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies".CELL 187.1(2024):49. |
入库方式： OAI收割
来源：上海药物研究所
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