Single-cell RNA sequencing reveals the process of CA19-9 production and dynamics of the immune microenvironment between CA19-9 (+) and CA19-9 (−) PDAC  

作　　者：Deyu Zhang Fang Cui Kailian Zheng Wanshun Li Yue Liu Chang Wu Lisi Peng Zhenghui Yang Qianqian Chen Chuanchao Xia Shiyu Li Zhendong Jin Xiaojiang Xu Gang Jin Zhaoshen Li Haojie Huang 

机构地区：[1]Department of Gastroenterology,Changhai Hospital,Naval Medical University,Shanghai 200433,China [2]Department of Pancreatic Surgery,Changhai Hospital,Naval Medical University,Shanghai 200433,China [3]College of Life Science,Fujian Agriculture and Forestry University,Fuzhou,Fujian 350000,China [4]Department of Pathology and Laboratory Medicine,Tulane University,New Orleans,LA 70115 USA [5]School of Medicine,Tulane University,New Orleans,LA 70115 USA.

出　　处：《Chinese Medical Journal》2024年第20期2415-2428,共14页中华医学杂志(英文版)

基　　金：supported by grants from the National Natural Science Foundation.The project was supported by the Major International(Regional)Joint Research Program of China(Grant No.82020108005);the Science Fund for Outstanding Young Scholars of China(Grant No.82022008).

摘　　要：Background:Pancreatic ductal adenocarcinoma(PDAC)is one of the main types of malignant tumor of the digestive system,and patient prognosis is affected by difficulties in early diagnosis,poor treatment response,and a high postoperative recurrence rate.Carbohydrate antigen 19-9(CA19-9)has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients.Nevertheless,the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.Methods:We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC(three CA19-9-positive and three CA19-9-negative PDAC samples)and two paracarcinoma samples.We also downloaded and integrated PDAC samples(each from three CA19-9-positive and CA19-9-negative patients)from an online database.The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence.Moreover,we built an in vitro coculture cellular model to confirm the potential function of CA19-9.Results:Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A,AQP5,and MUC5AC.CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts(apCAFs).Importantly,the proportion of immature ficolin-1 positive(FCN1+)macrophages was high in the CA19-9-negative group,and the proportion of mature M2-like macrophages was high in the CA19-9-positive group.High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis.Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment.Conclusions:Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC.CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

关 键 词：Carbohydrate antigen 19-9 CA19-9 Pancreatic ductal adenocarcinoma Single-cell RNA sequencing M2 macrophages Antigen-presenting cancer-associated fibroblast 

分 类 号：R73[医药卫生—肿瘤]