Pan-cancer and single-cell analyses reveal LAMP3 as a biomarker associated with cancer prognosis and immune infiltration

Abstract Background: Lysosomal-associated membrane protein 3 (LAMP3) is a member of the LAMP family and is also known as a marker of mature dendritic cells (DCs). However, it is unclear how the expression of LAMP3 is linked to human cancers or immune infiltration. Here, we conducted a systematic study on the function and mechanism of LAMP3 in pan-cancer. Methods: The expression level of LAMP3 was studied using the Sangerbox, TIMER 2.0, and GEPIA2 databases in various types of human cancer. The TCGA database and GEPIA2 were utilized to evaluate the potential of LAMP3 as a diagnostic and prognostic biomarker in pan-cancer. The LAMP3 mutation was analyzed using the cBioPortal database. The TIMER and TISIDB websites were used to investigate the role of LAMP3 in immune infiltration. We obtained single-cell RNA sequencing (scRNA-seq) data on immune cells from 75 patients diagnosed with one of the 13 most prevalent cancer types. Pseudotime analysis, GSVA, cellular interaction analysis, and TF analysis were performed using R. Results: Results showed that LAMP3 expression was elevated and mutated in the majority of tumors, indicating a worse prognosis. The ROC curve demonstrated that LAMP3 can serve as a diagnostic indicator. LAMP3 expression demonstrated a significant positive correlation with Treg infiltration levels, also showing a positive correlation with DC infiltration levels. Single-cell sequencing revealed that the expression of LAMP3 was concentrated in mature DC cells within tumor tissue. GSVA analysis found that NF-κB, apoptosis, and hypoxia were upregulated in this cluster of DC cells. These DC cells also exhibited high expression of various chemokines and were predicted to recruite Treg cells into tumor tissue through CCL17-CCR4 and CCL22-CCR4. Conclusion: LAMP3 may be a potential biomarker in pan-cancer, particularly in KIRC. Moreover, LAMP3 is associated with immune cell infiltration in pan-cancer and represents a potential immunotherapeutic target for tumor therapy.