A novel gene prognostic signature lymphocyte cytosolic protein 2 regulates melanoma progression by activating tumor-infiltrating CD8+ T-cells through the interferon regulatory factor 5 signaling pathway

Cutaneous malignant melanoma is the most lethal skin cancer. The advent of immunotherapy has revolutionized the status of clinical therapies of melanoma, which brought new hope to these patients. However, only a small proportion of patients are responders. Therefore, the identification of novel prognostic and immune-related biomarkers is crucial to guide the development of melanoma clinical treatments. Herein, RNA-seq data of the cutaneous melanoma from public database were used for identifying prognostic gene signatures, and we found that lymphocyte cytosolic protein 2 (LCP2) was highly expressed in melanoma patient, which was associated with better prognosis for melanoma. Kyoto Encyclopedia of Genes and Genomes and gene ontology analyses demonstrated that the differentially expressed genes are significantly involved in lysosome, B-cell receptor signaling pathways, Fc epsilon RI signaling pathway, and T-cell receptor signaling pathway, indicating that these signaling pathways play important roles in melanoma. LCP2 expression was positively correlated with CD8+ T-cell and the overall survival of melanoma patients, and this positive correlation was directly confirmed by fluorescence-activated cell sorting experiment. The in vivo experiment showed that LCP2 knockdown significantly promoted the melanoma progression and decreased interferon regulatory factor 5 (IRF5) expression. In conclusion, we identified that LCP2 is a possible prognostic gene signature for progression-free survival of melanoma patients and regulates melanoma progression by activating tumor-infiltrating CD8+ T-cells through the IRF5 signaling pathway, indicating that LCP2 could serve as a prognostic biomarker and therapeutic target in immunotherapy.