Deciphering the composition and key driver genes of breast invasive micropapillary carcinoma by multi-omics analysis
Yongjie Xie,
Ziyun Liu,
Jie Zhang,
Guangming Li,
Bo Ni,
Chunlei Shi,
Yiping Zou,
Yaoyao Zhou,
Xiaobin Shang
Affiliations
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
Ziyun Liu
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
Jie Zhang
Tianjin Medical University, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
Guangming Li
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 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
Chunlei Shi
Department of colorectal Surgery, The Wuhu Hospital of Traditional Chinese Medicine, Anhui, China
Yiping Zou
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; Corresponding author
Yaoyao Zhou
Tianjin Medical University, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Corresponding author
Xiaobin Shang
Department of Minimally Invasive Esophageal Surgery, 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, China; Corresponding author
Summary: In this study, we delved into the intrinsic cellular components and transcriptomic signatures characterizing breast-invasive micropapillary carcinoma (IMPC). Employing bulk RNA sequencing, we conducted differential gene expression and functional profiles across breast cancer tissues. Single-cell transcriptome sequencing was performed on mixed IMPC samples. Moreover, a multicenter retrospective cohort of IMPC patients validated the critical role of KRT80. Our findings illuminated heightened activity in redox reactions and metabolism-related functions within IMPC compared to other tissue types. The single-cell atlas of IMPC demonstrated substantial heterogeneity predominantly driven by two distinct cell subsets: epithelioid and interstitial cells. Pseudotime analysis unveiled unique cell trajectories, and we found positive correlation between KRT80 expression and clinicopathological characteristics in IMPC. High KRT80 expression was associated with shorter overall survival for IMPC patients. This investigation unmasked extensive heterogeneity within breast IMPC tumors, delineating lineage distinctions across diverse cell clusters. It unveils potential prospective therapeutic targets with clinical relevance.
