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@ARTICLE{Zhou:163272,
      author       = {Zhou, Lulin and Niu, Zubiao and Wang, Yuqi and Zheng, You
                      and Zhu, Yichao and Wang, Chenxi and Gao, Xiaoyan and Gao,
                      Lihua and Zhang, Wen and Zhang, Kaitai and Melino, Gerry and
                      Huang, Hongyan and Wang, Xiaoning and Sun, Qiang},
      title        = {{S}enescence as a dictator of patient outcomes and
                      therapeutic efficacies in human gastric cancer.},
      journal      = {Cell death discovery},
      volume       = {8},
      number       = {1},
      issn         = {2058-7716},
      address      = {London},
      publisher    = {Nature Publishing Group},
      reportid     = {DZNE-2022-00052},
      pages        = {13},
      year         = {2022},
      abstract     = {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.},
      cin          = {AG Nicotera},
      ddc          = {610},
      cid          = {I:(DE-2719)5000018},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35013121},
      pmc          = {pmc:PMC8748965},
      doi          = {10.1038/s41420-021-00769-6},
      url          = {https://pub.dzne.de/record/163272},
}