Deciphering the composition and key driver genes of breast invasive micropapillary carcinoma by multi-omics analysis

通过多组学分析揭示乳腺浸润性微乳头状癌的组成和关键驱动基因

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作者:Yongjie Xie, Ziyun Liu, Jie Zhang, Guangming Li, Bo Ni, Chunlei Shi, Yiping Zou, Yaoyao Zhou, Xiaobin Shang

Abstract

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.

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