Pancreatic cancer(PC)is a highly malignant neoplasm of the digestive system.The primary objective of this investigation is to elucidate the intricate mechanisms underlying the role of the aging process and the related...Pancreatic cancer(PC)is a highly malignant neoplasm of the digestive system.The primary objective of this investigation is to elucidate the intricate mechanisms underlying the role of the aging process and the related factor Epithelial membrane protein 1(EMP1)in PC progression.We established a prognostic model pertinent to the aging process that could be applied in postoperative PC patients.In vitro assays were employed to elucidate the impact of EMP1 on PC cell function.We employed lentiviral vectors for both knockdown and overexpression of EMP1 in Panc02 cells,followed by the establishment of subcutaneous,pulmonary metastasis,and orthotopic pancreatic liver metastasis models in mice.Using tissue microarrays,we evaluated the expression of EMP1 and its downstream entities,and then conducted clinical correlation analysis.A predictive Age-Related Score(ARS)system based on age-associated prognostic genes was developed,offering precise prognostic predictions for postoperative PC patients,which could be applied well at the single-cell level,showing diverse aging,epithelial–mesenchymal transition(EMT),cell migration,cell proliferation,and PI3K/AKT signaling activity in high and low ARS risk cells.EMP1 was identified as a pivotal molecule in the ARS system and is associated with poor prognosis.Besides,EMP1 could enhance the proliferation,migration,and invasion of PC cells both in vitro and in vivo by augmenting the PI3K/AKT signaling cascade.In essence,this research formulated an aging-centric prognostic model for postoperative PC and pinpointed EMP1 as an oncogenic factor facilitating tumor cell EMT during the aging trajectory in resectable PC patients.展开更多
基金sponsored by Natural Science Foundation of Chongqing,China(No.CSTB2022NSCQ-MSX1339 to J.F.Z.CSTB2022NSCQ-MSX1273 to J.Y.G.),Foundation of Key Laboratory of Tumor Immunology and Pathology(Army Medical University)+3 种基金Ministry of Education(No.2023jsz910 to J.F.Z.)National Natural Science Foundation of China(No.82203165 to J.Y.G.,82072723,82103249 to H.Z.W.)Chongqing medical scientific research project(Joint project of Chongqing Health Commission and Science and Technology Bureau)(No.2022MSXM031 to J.F.X.)Chongqing Technology Innovation and Application Development Special Key Project(No.CSTB2022TIAD-KPX0170 to H.Z.W.).
文摘Pancreatic cancer(PC)is a highly malignant neoplasm of the digestive system.The primary objective of this investigation is to elucidate the intricate mechanisms underlying the role of the aging process and the related factor Epithelial membrane protein 1(EMP1)in PC progression.We established a prognostic model pertinent to the aging process that could be applied in postoperative PC patients.In vitro assays were employed to elucidate the impact of EMP1 on PC cell function.We employed lentiviral vectors for both knockdown and overexpression of EMP1 in Panc02 cells,followed by the establishment of subcutaneous,pulmonary metastasis,and orthotopic pancreatic liver metastasis models in mice.Using tissue microarrays,we evaluated the expression of EMP1 and its downstream entities,and then conducted clinical correlation analysis.A predictive Age-Related Score(ARS)system based on age-associated prognostic genes was developed,offering precise prognostic predictions for postoperative PC patients,which could be applied well at the single-cell level,showing diverse aging,epithelial–mesenchymal transition(EMT),cell migration,cell proliferation,and PI3K/AKT signaling activity in high and low ARS risk cells.EMP1 was identified as a pivotal molecule in the ARS system and is associated with poor prognosis.Besides,EMP1 could enhance the proliferation,migration,and invasion of PC cells both in vitro and in vivo by augmenting the PI3K/AKT signaling cascade.In essence,this research formulated an aging-centric prognostic model for postoperative PC and pinpointed EMP1 as an oncogenic factor facilitating tumor cell EMT during the aging trajectory in resectable PC patients.
