Open Access

ARTICLE

ScRNA-seq reveals the correlation between M2 phenotype of tumor-associated macrophages and lymph node metastasis of breast cancer

JUN SHEN^1,#, HONGFANG MA^2,#, YONGXIA CHEN³, JIANGUO SHEN^1,*

1 Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
2 Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
3 Laboratory of Cancer Biology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China

* Corresponding Author: JIANGUO SHEN. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: Role of Reactive Oxygen Species and DNA Damage in Tumor Immunological Responses)

Oncology Research 2023, 31(6), 955-966. https://doi.org/10.32604/or.2023.029638

Received 28 February 2023; Accepted 18 July 2023; Issue published 15 September 2023

Abstract

The process of lymphatic metastasis was proved to be associated with podoplanin-expressing macrophages in breast cancer (BC). This study aimed to investigate the role of the M2 phenotype of tumor-associated macrophages and mine the key M2 macrophages-related genes for lymph node metastasis in BC. We downloaded the GSE158399 dataset from the Gene Expression Omnibus (GEO) database, which includes transcriptomic profiles of individual cells from primary tumors, negative lymph nodes (NLNs), and positive lymph nodes (PLNs) of breast cancer patients. The cell subsets were identified by clustering analysis after quality control of the scRNA-seq using Seurat. The activation and migration capability of M2 macrophages were evaluated with R package “GSVA”. The key M2 macrophages-related genes were screened from the differential expressed genes (DEGs) and M2 macrophages activation and migration gene sets collected from MSigDB database. Our analysis identified three main cell types in primary tumors, NLNs, and PLNs: basal cells, luminal cells, and immune cell subsets. The further cell type classification of immune cell subsets indicated M2 macrophages accumulation in NLs and PLs. The GSVA enrichment scores for activation and migration capability were increased significantly in M2 macrophages from primary tumors than NLNs and PLNs (p-value < 0.001). Seven M2 macrophages activation-related and 15 M2 macrophages migration-related genes were significantly up-regulated in primary tumors than NLNs and PLNs. The proportion and GSVA enrichment scores for activation and migration of M2 macrophages may be potential markers for lymph node metastasis in breast cancer. Our study demonstrated that twenty-two up-regulated mRNA may be possible therapeutic targets for lymph node metastasis in breast cancer.

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