Abstract
Background: Lymphoid-restricted membrane protein (LRMP) is an endoplasmic reticulum-associated protein that is expressed in a developmentally regulated manner in both B and T cell lineages. However, the role of LRMP in the growth, prognosis and immune infiltration in lung adenocarcinoma (LUAD) remains unclear. Method: The expression levels of LRMP mRNA in tumor and normal tissues were analyzed using Tumor Immune Estimation Resource 2.0 (TIMER 2.0) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2). LRMP protein expression was examined using the Human Protein Atlas. In vitro experiments, including qRT-PCR Western blot and immunohistochemistry staining were also performed to investigate LRMP expression. GEPIA2 and Kaplan-Meier plotter databases were used to analyze the clinical prognostic significance of LRMP. To further confirm the underlying function of LRMP, the data were analyzed using gene set enrichment analysis. Moreover, we also constructed plasmids to overexpress LRMP and explored the effect of LRMP in A549 cell line. Additionally, Tumor Immune single-cell Hub was used to investigate the distribution of LRMP in the LUAD immune microenvironment; TIMER and CIBERSORT were used to investigate the relationships among LRMP, LRMP co-expressed genes, and tumor-infiltrating immune cells; Finally, the correlations between LRMP and immune checkpoints were analyzed using TIMER 2.0. Results: The expression of LRMP was significantly lower in LUAD tissues and cell lines. High LRMP expression is associated with a better prognosis in patients with LUAD. In vitro experimental studies demonstrated that overexpression of LRMP could decrease the proliferation, migration and invasion in A549 cells, and downregulated multiple oncogenic signaling pathways, including p-STAT3, p-PI3K-p-AKT, p-MEK and EMT pathways. GSEA results showed that immuno-related and cell adhesion pathways were enriched in samples with high LRMP expression. LRMP and its co-expressed genes were positively correlated with various tumor-infiltrating immune cells and their markers. Additionally, LRMP positively correlated with immune checkpoints. Conclusions: Our data suggest that LRMP may act as a tumor suppressor gene and indicates a better prognosis. Moreover, LRMP is associated with immune infiltrates which may be involved in immunotherapy response in LUAD. Further studies are needed to validate these findings.
Highlights
Lung cancer is the second most common type of cancer in 2020 and is the leading cause of cancer-related deaths, accounting for approximately one in 10 cancers diagnosed and one in five deaths (Sung et al, 2021)
Our data suggest that Lymphoid-restricted membrane protein (LRMP) may act as a tumor suppressor gene and indicates a better prognosis
LRMP in Lung Adenocarcinoma may be involved in immunotherapy response in lung adenocarcinoma (LUAD)
Summary
Lung cancer is the second most common type of cancer in 2020 and is the leading cause of cancer-related deaths, accounting for approximately one in 10 cancers diagnosed and one in five deaths (Sung et al, 2021). Eighty-four percent of lung cancers are non-small cell lung cancers (NSCLCs), and only 20–30% of newly diagnosed lung tumors can be treated with radical surgery (Noone et al, 2018). Immunotherapy, such as programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated antigen 4 inhibitors, have shown promising results in melanoma, renal cancer, NSCLC, and other tumors (Garon et al, 2015; Larkin et al, 2015; Motzer et al, 2015). The role of LRMP in the growth, prognosis and immune infiltration in lung adenocarcinoma (LUAD) remains unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
