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Integration Analysis of Single-Cell Multi-Omics Reveals Prostate Cancer Heterogeneity.
Bian, Xiaojie; Wang, Wenfeng; Abudurexiti, Mierxiati; Zhang, Xingming; Ma, Weiwei; Shi, Guohai; Du, Leilei; Xu, Midie; Wang, Xin; Tan, Cong; Sun, Hui; He, Xiadi; Zhang, Chenyue; Zhu, Yao; Zhang, Min; Ye, Dingwei; Wang, Jianhua.
Afiliación
  • Bian X; Department of Urology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • Wang W; Cancer Institute, Shanghai Urological Cancer Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • Abudurexiti M; Cancer Institute, Shanghai Urological Cancer Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • Zhang X; Cancer Institute, Shanghai Urological Cancer Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • Ma W; Department of Urology, Shanghai Pudong New Area Gongli Hospital, Shanghai, 200135, China.
  • Shi G; Cancer Institute, Shanghai Urological Cancer Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • Du L; Department of Urology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • Xu M; Cancer Institute, Shanghai Urological Cancer Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • Wang X; Department of Urology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • Tan C; Cancer Institute, Shanghai Urological Cancer Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • Sun H; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
  • He X; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
  • Zhang C; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
  • Zhu Y; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
  • Zhang M; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
  • Ye D; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
  • Wang J; Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Adv Sci (Weinh) ; 11(18): e2305724, 2024 May.
Article en En | MEDLINE | ID: mdl-38483933
ABSTRACT
Prostate cancer (PCa) is an extensive heterogeneous disease with a complex cellular ecosystem in the tumor microenvironment (TME). However, the manner in which heterogeneity is shaped by tumors and stromal cells, or vice versa, remains poorly understood. In this study, single-cell RNA sequencing, spatial transcriptomics, and bulk ATAC-sequence are integrated from a series of patients with PCa and healthy controls. A stemness subset of club cells marked with SOX9highARlow expression is identified, which is markedly enriched after neoadjuvant androgen-deprivation therapy (ADT). Furthermore, a subset of CD8+CXCR6+ T cells that function as effector T cells is markedly reduced in patients with malignant PCa. For spatial transcriptome analysis, machine learning and computational intelligence are comprehensively utilized to identify the cellular diversity of prostate cancer cells and cell-cell communication in situ. Macrophage and neutrophil state transitions along the trajectory of cancer progression are also examined. Finally, the immunosuppressive microenvironment in advanced PCa is found to be associated with the infiltration of regulatory T cells (Tregs), potentially induced by an FAP+ fibroblast subset. In summary, the cellular heterogeneity is delineated in the stage-specific PCa microenvironment at single-cell resolution, uncovering their reciprocal crosstalk with disease progression, which can be helpful in promoting PCa diagnosis and therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Análisis de la Célula Individual / Microambiente Tumoral Límite: Humans / Male Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Análisis de la Célula Individual / Microambiente Tumoral Límite: Humans / Male Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania