Abstract 23P
Background
Lung cancer is a leading cause of mortality globally, particularly the subtype called lung adenocarcinoma (LUAD). Current treatments have limited success, emphasizing the need for better therapies. Heparan sulfate proteoglycans (HSPGs) and heparanase (Hpse) play important roles in cancer progression, including LUAD, but their exact functions are not fully understood. Our study aims to explore Hpse's relevance in LUAD progression and its effects on tumor cells.
Methods
We introduced shRNAs by lentiviral transfections against heparanase into a murine and a human cell line. We performed intravenous and orthotopic injections to assess the effects of our genetic perturbations on tumor growth, survival, and the tumor immune microenvironment.
Results
The study investigated the correlation between heparanase mRNA expression and overall survival in LUAD patients. Using the PRECOGG database and the Cancer Genome Atlas, we found that elevated HPSE expression correlated with poor overall survival in LUAD patients. Additionally, in vitro experiments demonstrated that heparanase promoted migration and invasion of lung cancer cells, suggesting its role in metastasis. Moreover, in vivo studies using mouse models showed that Hpse knockdown reduced tumor growth and metastasis and increased the survival of mice. Spectral flow cytometry analysis revealed many changes in the immune microenvironment between tumors with high and low Hpse expression, with significant alterations in myeloid and lymphoid cell populations. Notably, in Hpsel-low tumors, alveolar macrophages were more abundant. Surprisingly, these macrophages displayed an anti-tumorigenic phenotype characterized based on single-cell sequencing performed on leukocytes.
Conclusions
To conclude, our findings support our clinical analysis revealing that heparanase should be investigated further as a therapeutic target for patients with LUAD. More effort should be put towards inhibitors and trials should focus on this patient population that is in dire need of novel treatment options.
Editorial acknowledgement
Clinical trial identification
Legal entity responsible for the study
The authors.
Funding
CIHR.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
104P - Hypomethylated immune gene promoters as potential biomarkers in oral and oropharyngeal cancer
Presenter: Petra Anić
Session: Cocktail & Poster Display session
Resources:
Abstract
105P - Implementation of technical improvements in cfMeDIP-Seq library preparation
Presenter: Martina Dameri
Session: Cocktail & Poster Display session
Resources:
Abstract
106P - Clinical application of next-generation sequencing in metastatic colorectal cancer (mCRC): Experience from a comprehensive cancer centre
Presenter: David Lluís Garulo
Session: Cocktail & Poster Display session
Resources:
Abstract
107P - Unveiling mismatch repair deficiency (dMMR) and microsatellite-instability high (MSI-H) detection in cancer patients (pt) using a next-generation sequencing (NGS)-based molecular pre-screening program (MPP)
Presenter: Lucia Notario Rincon
Session: Cocktail & Poster Display session
Resources:
Abstract
108P - Validation and implementation of a large NGS panel to test liquid biopsies from patients with suspected advanced non-small cell lung cancer (NSCLC) in an NHS genomic laboratory for the QuicDNA biomarker study
Presenter: Rachel Dodds
Session: Cocktail & Poster Display session
Resources:
Abstract
109P - A multiomic, single-cell measurable residual disease (scMRD) assay for phasing DNA mutations and surface immunophenotypes
Presenter: Simone Formisano
Session: Cocktail & Poster Display session
Resources:
Abstract
110P - Multicellular three-dimensional tumor spheroid of nasopharyngeal carcinoma
Presenter: Shiau Chuen Cheah
Session: Cocktail & Poster Display session
Resources:
Abstract
111P - Development of digital PCR for accurate measurement of HER2 amplification in 184 gastric cancer patients
Presenter: So Young Kang
Session: Cocktail & Poster Display session
Resources:
Abstract
112P - A novel methylation-sensitive assay for early detection of hepatocellular carcinoma to improve surveillance
Presenter: Jeong Sil Ha
Session: Cocktail & Poster Display session
Resources:
Abstract
113P - Evaluation of effects of tissue preservation methods on the proteome abundance through deep proteomics of breast cancer tissue
Presenter: Shashwati parihari
Session: Cocktail & Poster Display session
Resources:
Abstract