Abstract

Lymphoid-restricted membrane protein (LRMP), also known as Jaw1, is an endoplasmic reticulum-associated protein that is expressed in a developmentally regulated fashion in both the B and T cell lineages. However, the relationship between LRMP and prognosis of lung adenocarcinoma (LUAD) and tumor-infiltrating lymphocytes remains unclear. The expression levels of LRMP mRNA in tumor and normal tissues were analyzed via Tumor Immune Estimation Resource2.0 (TIMER2.0) and Gene Expression Profiling Interactive Analysis2 (GEPIA2). LRMP protein expression was examined in The Human Protein Atlas (HPA). The association between LRMP expression and clinicopathological variables was analyzed using Pearson chi-squared test. GEPIA2 and Kaplan–Meier plotter databases were used to analyzed the clinical prognostic significance of LRMP. To further confirm the underlying function of LRMP, the data were analyzed by gene set enrichment analysis. In addition, Tumor Immune single-cell Hub (TISCH) 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 with TIMER 2.0. The expression of LRMP was significantly low in LUAD, and correlated with vital status, age, gender, TNM stage, new tumor event type of LUAD patients. High LRMP expression was related to a better prognosis in patients with LUAD. GSEA results showed that immuno-related and cell adhesion pathways were enriched in samples with high LRMP expression. In LUAD tumor immune microenvironment, LRMP was mainly distributed in tumor infiltrating immune cells. TIMER and CIBERSORT results showed that LRMP and its co-expressed genes were positively correlated with various tumor infiltrating immune cells and their markers. In addition, LRMP was positively correlated with immune checkpoints. In conclusion, LRMP expression was significantly reduced in LUAD patients, which indicated a poor prognosis. The expression of LRMP was significantly associated to the levels of immune cell infiltration and immune checkpoints expression. Therefore, LRMP may be used as a prognostic biomarker and as an indicator of immunotherapy response. Further studies need to validate our findings.

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