Research Paper Volume 13, Issue 16 pp 20836—20852
Heparanase is a novel biomarker for immune infiltration and prognosis in breast cancer
- 1 Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China
Received: October 19, 2020 Accepted: April 29, 2021 Published: August 30, 2021
https://doi.org/10.18632/aging.203489How to Cite
Copyright: © 2021 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Heparanase (HPSE), an endoglycosidase that cleaves heparan sulfate, regulates a variety of biological processes that promote tumor progression. In this study, we analyzed the correlation between HPSE expression and prognosis in cancer patients, using multiple databases (Oncomine, TIMER, PrognoScan, GEPIA, Kaplan–Meier plotter, miner v4.1, DAVID). HPSE expression was significantly increased in bladder, breast, lung, and stomach cancer compared to matched normal tissues. The increased HPSE expression correlated with poor prognosis and increased immune infiltration levels of B cells, CD8+ and CD4+ T cells, macrophages, neutrophils and dendritic cells in bladder and breast cancer. In breast cancer, the high HPSE expression was associated with basal-like subtypes, younger age (0-40), advanced Scarff-Bloom-Richardson grade, Nottingham Prognostic Index and p53 mutation status. In addition, using a mouse model of breast cancer, our data showed that HPSE upregulated IL-10 expression and promoted macrophage M2 polarization and T cell exhaustion. Together, our data provide a novel immunological perspective on the mechanisms underlying breast cancer progression, and indicate that HPSE may serve as a biomarker for immune infiltration and prognosis in breast cancer.
Abbreviations
HPSE: heparanase; CTLA4: cytotoxic T lymphocyte associated antigen 4; PD-1: programmed death-1; PD-L1: programmed death ligand-1; NSCLC: non-small-cell lung carcinoma; TILs: tumor-infiltrating lymphocytes; TME: Tumor microenvironment; HS: heparan sulfate; GO: gene ontology; BLCA: bladder urothelial carcinoma; BRCA: breast invasive carcinoma; CHOL: cholangiocarcinoma; ESCA: esophageal carcinoma; LUAD: lung adenocarcinoma; LUSC: Lung squamous carcinoma; STAD: stomach adenocarcinoma; THCA: thyroid carcinoma; COAD: colon adenocarcinoma; HNSC: head and neck cancer; KIRC: kidney renal clear cell carcinoma; KICH: kidney chromophobe; LIHC: liver hepatocellular carcinoma; PRAD: prostate adenocarcinoma; READ: rectum adenocarcinoma; UCEC: uterine corpus endometrial carcinoma; SBR: Scarff–Bloom–Richardson; NPI: Nottingham Prognostic Index; Akt: phosphorylation of protein kinase B; ERK: extracellular regulated protein kinase; CXCL2: C-X-C motif chemokine ligand 2; VEGF: vascular endothelial growth factor; MSR-2: macrophage scavenger receptor-2; IBD: inflammatory bowel disease; TLRs: Toll-like receptors; TCGA: The Cancer Genome Atlas; OS: overall survival; RFS: relapse-free survival; DMFS: distant metastasis-free survival; DSS: disease-specific survival; DFS: disease-free survival; HR: hazard ratio; GEPIA: Gene Expression Profiling Interactive Analysis; DCs: dendritic cells; H-score: Histochemical score.