Kaisa Cui1,2, Surui Yao1, Bingxin Liu1,2, Shengbai Sun1,2, Liang Gong2,3, Qilin Li4, Bojian Fei5, Zhaohui Huang6,7. 1. Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, 214062, Wuxi, Jiangsu, China. 2. Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, 214122, Wuxi, Jiangsu, China. 3. Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 214122, Wuxi, Jiangsu, China. 4. Computer Vision Lab, Department of Electrical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA. 5. Department of Surgical Oncology, Affiliated Hospital of Jiangnan University, 214122, Wuxi, Jiangsu, China. wx4yfbj@163.com. 6. Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, 214062, Wuxi, Jiangsu, China. zhaohuihuang@jiangnan.edu.cn. 7. Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, 214122, Wuxi, Jiangsu, China. zhaohuihuang@jiangnan.edu.cn.
Abstract
BACKGROUND: Gastric cancer (GC) is characterised by a heterogeneous tumour microenvironment (TME) that is closely associated with the response to treatment, especially immunotherapies. However, most previous GC molecular subtyping systems need complex gene signatures and examination methods, restricting their clinical applications. Thus, we developed a new TME-based molecular subtype using only two genes. METHODS: Nine independent GC cohorts at the tissue- or single-cell level with more than 2000 patients were used in this study, including data we examined by single-cell sequencing, quantitative RT-PCR and immunochemistry/immunofluorescence staining. Nine different methods, five existing molecular subtypes and a series of signatures were used to evaluate the TME and molecular characteristics of GC. RESULTS: We established a CTSL/ZBTB7B subtyping system and uncovered the novel CTSLHighZBTB7BLow high-risk subgroup, but characterised by relative higher immune cell infiltration and lower tumour purity. This subgroup demonstrate higher levels of immune checkpoints and more enrichment of cancer-related pathways compared with other cases. CONCLUSIONS: We identified a high-risk subpopulation with unique TME features based on expressions of CTSL and ZBTB7B, suggesting a counterbalancing phenotype between immunostimulatory and immunosuppressive mechanisms. This subtyping system could be used to select treatment and management strategies for GC.
BACKGROUND: Gastric cancer (GC) is characterised by a heterogeneous tumour microenvironment (TME) that is closely associated with the response to treatment, especially immunotherapies. However, most previous GC molecular subtyping systems need complex gene signatures and examination methods, restricting their clinical applications. Thus, we developed a new TME-based molecular subtype using only two genes. METHODS: Nine independent GC cohorts at the tissue- or single-cell level with more than 2000 patients were used in this study, including data we examined by single-cell sequencing, quantitative RT-PCR and immunochemistry/immunofluorescence staining. Nine different methods, five existing molecular subtypes and a series of signatures were used to evaluate the TME and molecular characteristics of GC. RESULTS: We established a CTSL/ZBTB7B subtyping system and uncovered the novel CTSLHighZBTB7BLow high-risk subgroup, but characterised by relative higher immune cell infiltration and lower tumour purity. This subgroup demonstrate higher levels of immune checkpoints and more enrichment of cancer-related pathways compared with other cases. CONCLUSIONS: We identified a high-risk subpopulation with unique TME features based on expressions of CTSL and ZBTB7B, suggesting a counterbalancing phenotype between immunostimulatory and immunosuppressive mechanisms. This subtyping system could be used to select treatment and management strategies for GC.
Authors: Yan Lan; Mahmoud Moustafa; Maximilian Knoll; Chunxiao Xu; Jennifer Furkel; Adam Lazorchak; Tsz-Lun Yeung; Sayed-Mohammad Hasheminasab; Molly H Jenkins; Sarah Meister; Huakui Yu; Julian Schlegel; Bo Marelli; Zili Tang; Guozhong Qin; Carmen Klein; Jin Qi; Cheng Zhou; George Locke; Damir Krunic; Melissa G Derner; Christian Schwager; Rachel E Fontana; Katharina Kriegsmann; Feng Jiang; Katrin Rein; Mark Kriegsmann; Juergen Debus; Kin-Ming Lo; Amir Abdollahi Journal: Cancer Cell Date: 2021-09-09 Impact factor: 31.743
Authors: Francesca Finotello; Clemens Mayer; Christina Plattner; Gerhard Laschober; Dietmar Rieder; Hubert Hackl; Anne Krogsdam; Zuzana Loncova; Wilfried Posch; Doris Wilflingseder; Sieghart Sopper; Marieke Ijsselsteijn; Thomas P Brouwer; Douglas Johnson; Yaomin Xu; Yu Wang; Melinda E Sanders; Monica V Estrada; Paula Ericsson-Gonzalez; Pornpimol Charoentong; Justin Balko; Noel Filipe da Cunha Carvalho de Miranda; Zlatko Trajanoski Journal: Genome Med Date: 2019-05-24 Impact factor: 15.266