Revealing splenectomy-driven microRNA hsa-7b-5p’s role in pancreatic cancer progression
Liangliang Wu,
Yongjie Xie,
Bo Ni,
Peng Jin,
Bin Li,
Mingzhi Cai,
Baogui Wang,
Chengyan Wu,
Yuexiang Liang,
Xiaona Wang
Affiliations
Liangliang Wu
Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
Yongjie Xie
Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
Bo Ni
Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
Peng Jin
Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
Bin Li
Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
Mingzhi Cai
Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
Baogui Wang
Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
Chengyan Wu
Department of Bioinformation, Beijing University of Technology, Beijing 100124, China
Yuexiang Liang
Department of Gastrointestinal Oncology, The First Affiliated Hospital of Hainan Medical University, Longhua Road, Longhua District, Haikou 570102, China
Xiaona Wang
Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China; Corresponding author
Summary: Splenectomy often accompanies distal pancreatectomy for pancreatic cancer. However, debates persist on splenic function loss impact. Prior studies in mice revealed splenectomy promotes pancreatic cancer growth by altering CD4/Foxp3 and CD8/Foxp3 ratios. The effect on other immune cells remains unclear. Clinical observations indicate splenectomy induces immunosuppression, heightening recurrence and metastasis risk. Here, we established an orthotopic pancreatic cancer model with splenectomy and observed a significant increase in tumor burden. Flow cytometry revealed elevated MDSCs, CD8+PD-1high+ T cells, and reduced CD4+ T cells, CD8+ T cells, and natural killer cells in tumors. Bulk sequencing identified increased MicroRNA (miRNA) hsa-7b-5p post-splenectomy, correlating with staging and immunosuppression. Similar results were obtained in vivo by constructing a KPC-miRNA hsa-7b-5p-sh cell line. These findings suggest that splenectomy enhances the expression of miRNA hsa-7b-5p, inhibits the tumor immune microenvironment, and promotes pancreatic cancer growth.
