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Evolution of immune and stromal cell states and ecotypes during gastric adenocarcinoma progression.
Wang, Ruiping; Song, Shumei; Qin, Jiangjiang; Yoshimura, Katsuhiro; Peng, Fuduan; Chu, Yanshuo; Li, Yuan; Fan, Yibo; Jin, Jiankang; Dang, Minghao; Dai, Enyu; Pei, Guangsheng; Han, Guangchun; Hao, Dapeng; Li, Yating; Chatterjee, Deyali; Harada, Kazuto; Pizzi, Melissa Pool; Scott, Ailing W; Tatlonghari, Ghia; Yan, Xinmiao; Xu, Zhiyuan; Hu, Can; Mo, Shaowei; Shanbhag, Namita; Lu, Yang; Sewastjanow-Silva, Matheus; Fouad Abdelhakeem, Ahmed Adel; Peng, Guang; Hanash, Samir M; Calin, George A; Yee, Cassian; Mazur, Pawel; Marsden, Autumn N; Futreal, Andrew; Wang, Zhenning; Cheng, Xiangdong; Ajani, Jaffer A; Wang, Linghua.
Afiliação
  • Wang R; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Song S; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Qin J; Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China; Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, Zhejiang 310018, China.
  • Yoshimura K; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Peng F; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Chu Y; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Li Y; Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang 110001, China.
  • Fan Y; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Jin J; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Dang M; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Dai E; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Pei G; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Han G; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Hao D; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Li Y; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Chatterjee D; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Harada K; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Pizzi MP; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Scott AW; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Tatlonghari G; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Yan X; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Xu Z; Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
  • Hu C; Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
  • Mo S; Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
  • Shanbhag N; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Lu Y; Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Sewastjanow-Silva M; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Fouad Abdelhakeem AA; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Peng G; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Hanash SM; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Calin GA; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Yee C; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Mazur P; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Marsden AN; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Futreal A; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Wang Z; Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang 110001, China.
  • Cheng X; Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China; Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, Zhejiang 310018, China.
  • Ajani JA; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: jajani@mdanderson.org.
  • Wang L; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences (GSBS), Houston, TX 77030, USA. Electronic address: lwang22@mdanderson.org.
Cancer Cell ; 41(8): 1407-1426.e9, 2023 08 14.
Article em En | MEDLINE | ID: mdl-37419119
ABSTRACT
Understanding tumor microenvironment (TME) reprogramming in gastric adenocarcinoma (GAC) progression may uncover novel therapeutic targets. Here, we performed single-cell profiling of precancerous lesions, localized and metastatic GACs, identifying alterations in TME cell states and compositions as GAC progresses. Abundant IgA+ plasma cells exist in the premalignant microenvironment, whereas immunosuppressive myeloid and stromal subsets dominate late-stage GACs. We identified six TME ecotypes (EC1-6). EC1 is exclusive to blood, while EC4, EC5, and EC2 are highly enriched in uninvolved tissues, premalignant lesions, and metastases, respectively. EC3 and EC6, two distinct ecotypes in primary GACs, associate with histopathological and genomic characteristics, and survival outcomes. Extensive stromal remodeling occurs in GAC progression. High SDC2 expression in cancer-associated fibroblasts (CAFs) is linked to aggressive phenotypes and poor survival, and SDC2 overexpression in CAFs contributes to tumor growth. Our study provides a high-resolution GAC TME atlas and underscores potential targets for further investigation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Lesões Pré-Cancerosas / Neoplasias Gástricas / Adenocarcinoma / Fibroblastos Associados a Câncer Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Lesões Pré-Cancerosas / Neoplasias Gástricas / Adenocarcinoma / Fibroblastos Associados a Câncer Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos