A novel prognostic biomarker LCP2 correlates with metastatic melanoma-infiltrating CD8+ T cells

Abstract

Abstract Lymphocyte cytosolic protein 2 (LCP2) is one of the SLP-76 family of adapters, which are critical intermediates in signal cascades downstream of several receptors. LCP2 regulates immunoreceptor signaling (such as T-cell receptors) and is also required for integrin signaling in neutrophils and platelets. However, the role of LCP2 in the tumor microenvironment is still unknown. In this study, we found a significant increase of mRNA and protein expression of LCP2 in metastatic skin cutaneous melanoma compared to normal skin. The upregulation of LCP2 was associated with good overall survival of patients with metastatic skin cutaneous melanoma, who received pharmacotherapy and radiation. GSEA signaling pathways analysis showed that LCP2 was involved in multiple pathways of immune response and correlation analysis revealed LCP2 was positively correlated with molecules in TCR signaling and 11 immune checkpoints, while LCP2 negatively correlated with 2 immune checkpoints in the metastatic skin cutaneous melanoma. According to the different expressions of LCP2, high LCP2 expression was positively correlated with more tumor-infiltrating CD8+ T cells. Furthermore, Kaplan–Meier plot indicated that LCP2 acted as a prognostic biomarker for progression-free survival of patients with metastatic skin cutaneous melanoma receiving anti-PD1 immunotherapy. In conclusion, our results integrated both the expression and function of LCP2 in melanoma using multiple tools, shedding light on the potential role of LCP2 in melanoma, and suggesting LCP2 serves as a prognostic biomarker and therapeutic target in anti-tumor immunity.