TY  - JOUR
AU  - Zhou, Lulin
AU  - Niu, Zubiao
AU  - Wang, Yuqi
AU  - Zheng, You
AU  - Zhu, Yichao
AU  - Wang, Chenxi
AU  - Gao, Xiaoyan
AU  - Gao, Lihua
AU  - Zhang, Wen
AU  - Zhang, Kaitai
AU  - Melino, Gerry
AU  - Huang, Hongyan
AU  - Wang, Xiaoning
AU  - Sun, Qiang
TI  - Senescence as a dictator of patient outcomes and therapeutic efficacies in human gastric cancer.
JO  - Cell death discovery
VL  - 8
IS  - 1
SN  - 2058-7716
CY  - London
PB  - Nature Publishing Group
M1  - DZNE-2022-00052
SP  - 13
PY  - 2022
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:35013121
C2  - pmc:PMC8748965
DO  - DOI:10.1038/s41420-021-00769-6
UR  - https://pub.dzne.de/record/163272
ER  -