Abstract P3-05-46: scRNA-seq profiling reveals different tumor immune-microenvironment in triple negative breast cancer and decodes pivotal role of THBS1- SDC1 axis in tumor metastasis

Abstract

Abstract ABSTRACT Background: Breast cancer has become the most common cancer worldwide and triple-negative breast cancer (TNBC) is the most aggressive subtype due to the lacks of hormone receptors and HER2 expression. Increasing rate of breast cancer metastasis also need to be solved. Nearly one in four breast cancer patients developed metastasis after treatment, which attributed to 90% cancer related death. Considering highly aggressive pattern of TNBC, TNBC showed higher metastasis probability rather than other subtypes. Therefore, exploring more biomarkers and therapeutic targets are on urgent. Methods: We profiled the transcriptomes of 59646 cells from 12 primary and 4 metastatic tumor samples from Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). Results: Comparing with primary site, metastatic site was predominated with immunosuppressive tumor microenvironment. In brief, metastatic samples showed increasing numbers of macrophages, lower anti-tumor microenvironment scores, higher malignant cell properties scores, less effective T cells and macrophages, enhanced immune escape potential tumor cells and a later pseudotime state of malignant cells, compared with primary samples. Remarkably, metastatic samples exhibited a stronger interaction of THBS1-SDC1 axis between macrophage subcluster named angiogenesis-1 and malignant cell subcluster named CDKN2A epithelial cells. We subsequently confirmed that higher THBS1-SDC1 expression indicated with poor overall survival and distant metastatic free survival of TNBC patients in The Cancer Genome Atlas (TCGA) TNBC cohort. Conclusion: Our immune landscape of TNBC ecosystem provide deeper insights into tumor metastasis and offer potential biomarkers and therapeutic target for TNBC. Key words: Breast cancer; immune-microenvironment; THBS1; SDC1; metastasis Citation Format: Liyi Zhang, Qi Zhang, Pei Li, Min Xiong, Yue Zhou, Jingyan Xue, Ming Chen, Wei-Ru Chi, Hengyu Ren, Chih Wan Goh, Douwaner Liu, Liren Wangxu, Yayun Chi, Bingqiu Xiu, Jiong Wu. scRNA-seq profiling reveals different tumor immune-microenvironment in triple negative breast cancer and decodes pivotal role of THBS1- SDC1 axis in tumor metastasis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-46.