Inhibiting immune escape in lung adenocarcinoma: the role of SPARC in suppressing CD276 function

Abstract

SPARC is an acidic, cysteine-rich, calcium-binding member of the non-collagen glycoproteins originating in bone. Although implicated in the development of several cancers, the functions and mechanisms of SPARC remain unclear. The aim of this study was to investigate whether smooth muscle cell (SMC)-associated SPARC acts an important tumour suppressor in lung adenocarcinoma (LUAD). SPARC inhibits immune evasion in LUAD by suppressing CD276 functionality. We downloaded RNA-sequencing data from patients with LUAD in The Cancer Genome Atlas and identified a set of genes showing SMC-specific expression in these samples. We then screened for differentially expressed genes (DEGs). Enrichment analysis using the Gene Expression Omnibus identified key genes, while immune pathway analysis explored the expression of immune checkpoints involved in LUAD immune regulation. We further validated the differential expression of SPARC and CD276 using immunohistochemistry. Among the upregulated DEGs, SPARC exhibited high enrichment in SMCs, whereas 13 immune checkpoints, such as LAIR1 and CTLA4, were excluded. The infiltration level of the CD276 immune checkpoint was lower in the high-risk group than in the low-risk group. While our results suggest a correlation between SPARC, CD276 and LUAD, additional studies are needed to validate these findings and elucidate the underlying mechanisms before definitive conclusions can be drawn regarding their utility in clinical practice.

Keywords:

• Lung adenocarcinoma
• immunology
• bioinformatics analysis
• biomarkers
• tumour microenvironment
• SPARC

Acknowledgments

The authors would like to thank Editage (www.editage.cn) for their English language editing.

Ethics approval

The Ethics Committee of The First Affiliated Hospital of Zhengzhou University provided ethical approval for the experiments involving human beings in this study ([2021]0139), which were guided by the Declaration of Helsinki.

Consent form

Written informed consent was obtained from the donors or their relatives.

Author contributions

Y Zhao: Formal analysis, Investigation, Visualization, Writing - Original Draft. HL: Methodology, Resources, Writing - Original Draft. Y Zhang: Conceptualization, Visualization, Methodology, Validation. ZY: Data curation, Formal analysis. XC: Data curation, Software. YY: Conceptualization, Project administration, Funding acquisition, Resources, Writing - Review & Editing, Supervision. All authors have read and approved the final version of the paper.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Anonymized data will be made available from the corresponding author [YY] upon reasonable request.

Additional information

Funding

This work was supported by the Leading Talent Cultivation Project of Henan Health Science and Technology Innovation Talents (grant number YXKC2021016), Henan Provincial College and University Research Project (grant number 22A320072), Henan Provincial Science and Technology Development Project (grant number SBGJ202102122), and the Henan Provincial Medical Education Research Project (grant number Wjlx2021279).