163272 20230915090515.0 10.1038/s41420-021-00769-6 doi pmid:35013121 pmid pmc:PMC8748965 pmc altmetric:120762540 altmetric DZNE-2022-00052 English 610 Zhou, Lulin 0 Senescence as a dictator of patient outcomes and therapeutic efficacies in human gastric cancer. London 2022 Nature Publishing Group article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1654865153_23357 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Senescence is believed to be a pivotal player in the onset and progression of tumors as well as cancer therapy. However, the guiding roles of senescence in clinical outcomes and therapy selection for patients with cancer remain obscure, largely due to the absence of a feasible senescence signature. Here, by integrative analysis of single cell and bulk transcriptome data from multiple datasets of gastric cancer patients, we uncovered senescence as a veiled tumor feature characterized by senescence gene signature enriched, unexpectedly, in the noncancerous cells, and further identified two distinct senescence-associated subtypes based on the unsupervised clustering. Patients with the senescence subtype had higher tumor mutation loads and better prognosis as compared with the aggressive subtype. By the machine learning, we constructed a scoring system termed as senescore based on six signature genes: ADH1B, IL1A, SERPINE1, SPARC, EZH2, and TNFAIP2. Higher senescore demonstrated robustly predictive capability for longer overall and recurrence-free survival in 2290 gastric cancer samples, which was independently validated by the multiplex staining analysis of gastric cancer samples on the tissue microarray. Remarkably, the senescore signature served as a reliable predictor of chemotherapeutic and immunotherapeutic efficacies, with high-senescore patients benefited from immunotherapy, while low-senescore patients were responsive to chemotherapy. Collectively, we report senescence as a heretofore unrecognized hallmark of gastric cancer that impacts patient outcomes and therapeutic efficacy. 351 - Brain Function (POF4-351) G:(DE-HGF)POF4-351 POF4-351 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Niu, Zubiao 1 Wang, Yuqi 2 Zheng, You 3 Zhu, Yichao 4 Wang, Chenxi 5 Gao, Xiaoyan 6 Gao, Lihua 7 Zhang, Wen 0000-0003-3150-2751 8 Zhang, Kaitai 9 Melino, Gerry P:(DE-2719)9001390 10 dzne Huang, Hongyan 0000-0001-8340-6660 11 Wang, Xiaoning 0000-0002-3762-7830 12 Sun, Qiang 0000-0002-5342-0637 13 10.1038/s41420-021-00769-6 Vol. 8, no. 1, p. 13 PERI:(DE-600)2842546-7 1 13 Cell death discovery 8 2022 2058-7716 OpenAccess http://pub.dzne.de/record/163272/files/DZNE-2022-00052.pdf OpenAccess pdfa http://pub.dzne.de/record/163272/files/DZNE-2022-00052.pdf?subformat=pdfa oai:pub.dzne.de:163272 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 10 P:(DE-2719)9001390 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-351 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Brain Function 0 2022 Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ 2021-05-04 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2021-05-04 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2021-05-04 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2021-05-04 Fees StatID:(DE-HGF)0700 StatID 2021-05-04 OpenAccess StatID:(DE-HGF)0510 StatID Article Processing Charges StatID:(DE-HGF)0561 StatID 2021-05-04 JCR StatID:(DE-HGF)0100 StatID CELL DEATH DISCOV : 2021 2023-03-31 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2023-03-31 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2023-03-31 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2021-02-14T16:19:13Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2021-02-14T16:19:13Z Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Blind peer review 2021-02-14T16:19:13Z DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2023-03-31 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2023-03-31 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2023-03-31 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2023-03-31 IF >= 5 StatID:(DE-HGF)9905 StatID CELL DEATH DISCOV : 2021 2023-03-31 I:(DE-2719)5000018 AG Nicotera Synaptic Connectivity and Neurodegeneration 0 journal VDB UNRESTRICTED I:(DE-2719)5000018 FullTexts