Integrated proteogenomic characterization of ampullary adenocarcinoma

Qiao Zhang; Xiaomeng Xu; Dongxian Jiang; Yunzhi Wang; Haixing Wang; Jiajun Zhu; Shaoshuai Tang; Ronghua Wang; Shuang Zhao; Kai Li; Jinwen Feng; Hang Xiang; Zhenmei Yao; Ning Xu; Rundong Fang; Wenjia Guo; Yu Liu; Yingyong Hou; Chen Ding

doi:10.1038/s41421-024-00742-4

Integrated proteogenomic characterization of ampullary adenocarcinoma

Cell Discov. 2025 Jan 7;11(1):2. doi: 10.1038/s41421-024-00742-4.

Authors

Qiao Zhang^#¹, Xiaomeng Xu^#¹, Dongxian Jiang^#², Yunzhi Wang^#¹, Haixing Wang^#², Jiajun Zhu¹, Shaoshuai Tang¹, Ronghua Wang³, Shuang Zhao³, Kai Li¹, Jinwen Feng¹, Hang Xiang¹, Zhenmei Yao¹, Ning Xu¹, Rundong Fang¹, Wenjia Guo⁴, Yu Liu⁵, Yingyong Hou⁶, Chen Ding^{7

8}

Affiliations

¹ Center for Cell and Gene Therapy, Clinical Research Center for Cell-based Immunotherapy, Shanghai Pudong Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, 200433, China.
² Department of Pathology, Zhongshan Hospital Fudan University, Shanghai, China.
³ Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Department of Hematology & Oncology, Shanghai Jiao Tong University, Shanghai, China.
⁴ Departments of Cancer Research Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Translational Biomedical Engineering, Urumqi, Xinjiang, China.
⁵ Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Department of Hematology & Oncology, Shanghai Jiao Tong University, Shanghai, China. liuyu@scmc.com.cn.
⁶ Department of Pathology, Zhongshan Hospital Fudan University, Shanghai, China. hou.yingyong@zs-hospital.sh.cn.
⁷ Center for Cell and Gene Therapy, Clinical Research Center for Cell-based Immunotherapy, Shanghai Pudong Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, 200433, China. chend@fudan.edu.cn.
⁸ Departments of Cancer Research Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Translational Biomedical Engineering, Urumqi, Xinjiang, China. chend@fudan.edu.cn.

^# Contributed equally.

Abstract

Ampullary adenocarcinoma (AMPAC) is a rare and heterogeneous malignancy. Here we performed a comprehensive proteogenomic analysis of 198 samples from Chinese AMPAC patients and duodenum patients. Genomic data illustrate that 4q loss causes fatty acid accumulation and cell proliferation. Proteomic analysis has revealed three distinct clusters (C-FAM, C-AD, C-CC), among which the most aggressive cluster, C-AD, is associated with the poorest prognosis and is characterized by focal adhesion. Immune clustering identifies three immune clusters and reveals that immune cluster M1 (macrophage infiltration cluster) and M3 (DC cell infiltration cluster), which exhibit a higher immune score compared to cluster M2 (CD4⁺ T-cell infiltration cluster), are associated with a poor prognosis due to the potential secretion of IL-6 by tumor cells and its consequential influence. This study provides a comprehensive proteogenomic analysis for seeking for better understanding and potential treatment of AMPAC.

Grants and funding

32330062/National Natural Science Foundation of China (National Science Foundation of China)