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Tumor Discovery LCP2 regulates melanoma progression

Keywords: Cutaneous melanoma; Lymphocyte cytosolic protein 2; Prognostic gene signature; Immunotherapies; Interferon
regulatory factor 5

1. Introduction the activation of T-cell, and IL-2 secretion subsequently
results in the release of cytokines that lead to apoptosis
Melanoma is known to be the most lethal type of skin cancer, of target cells [15,16] . Moreover, Siggs et al. found that the
with an estimated over 160,000 new cases diagnosed each mice with LCP2 mutation secreted excessive amounts
year [1,2] . Although melanoma constitutes <5% of all skin of proinflammatory cytokines, IgE, and autoantibodies,
cancers, 80% of skin cancer-related deaths are caused by suggesting that slight decrease in LCP2 expression is
melanoma. Despite great advances in biological research enough to trigger immune dysregulation . In a nutshell,
[17]
and therapeutic approaches in the past years, the morbidity LCP2 plays a significant important role in the immune
and mortality rates have still increased in the past half system. However, the specific role of LCP2 in the tumor
century . Due to high immunogenicity of melanoma, microenvironment is still obscure.
[2]
the recent breakthroughs achieved in immunotherapies
have revolutionized the way we treat melanoma, and this As melanoma exhibits high immunogenicity, we
has led to a dramatic improvement in the prognosis of the hypothesized that identifying immune-related genes that are
patients [3,4] . However, only a small proportion of patients associated with the occurrence and prognosis of melanoma
respond to these immunotherapies, which means that could help delineate the melanoma-specific mechanisms
the mechanism of interaction between immune system of immunoregulation, which may shed new light on
and melanoma invasion has not yet been fully elucidated. immunotherapy research. In the present study, the RNA-
Therefore, it is necessary to identify transcriptome seq data of cutaneous melanoma from the public database
signatures within tumor immune microenvironment that were used for identifying prognostic gene signatures, and
affects tumor progression and patient survival. we found that LCP2 was highly expressed in the patients
with melanoma. The expression of LCP2 was positively
Several studies have successfully identified transcriptome correlated with CD8 T-cell and the overall survival (OS)
+
signatures that could predict the survival of melanoma of melanoma patients, and this positive correlation was
patients [5,6] . These signatures could help discern melanoma directly confirmed by flow cytometry analysis. Moreover,
patients with high risk in advance and evaluate response to we further explored the potential mechanism of LCP2 in
certain therapeutic interventions. Few studies have explored tumor microenvironment of melanoma in vivo. Knockdown
the relationship between the immune gene expression and of LCP2 significantly promoted the progression of
the prognosis for melanoma. Zhao et al. identified a 25-gene melanoma and decreased the IRF5 expression. Based on
signature from immune cells-related genes though selecting our results, we identified that LCP2 is a possible prognostic
the genes with the highest correlation with the ImmuneScore gene signature for progressive-free survival of patients
that reflects leukocyte infiltration, and calculated leukocyte with melanoma, which repressed the growth of melanoma
infiltration score to predict the survival of melanoma through positively regulating the IRF5 signaling pathway
patients . However, not all 25 genes identified in this study followed by activation of CD8 T-cells and promotion of
[7]
+
may be associated with the development and progression of antitumor response.
melanoma.
2. Materials and methods
Lymphocyte cytosolic protein 2 (LCP2), one of the
SLP-76 family of adapters, is primarily expressed in Major immune pathways (N = 29) were retrieved from the
hematopoietic cells . In addition, LCP2 is also reported Reactome pathway database (https://reactome.org/) , which
[8]
[18]
to be expressed in platelets, macrophages, neutrophils, contains three main immune pathways including innate
mast cells, developing B-cells, and natural killer cells [8,9] . immune system, adaptive immune system, and cytokine
However, the current data showed that LCP2 is differentially signaling in immune system, and 2070 genes in total.
expressed in many different types of tumors and is correlated
with prognosis in gastric cancer, breast cancer , lung 2.1. Data sets used
[10]
adenocarcinoma, and metastatic melanoma patients. We used two expression profile data sets to identify
[12]
[11]
Furthermore, it has been reported that LCP2 is involved differentially expressed genes (DEGs) between melanomas
in T-cell-receptor signaling and is essential for normal and controls. These data sets are GSE3189 (including 45
[13]
T-cell development and activation . LCP2 can activate melanoma samples, 18 benign skin nevus samples, and
[14]
the promoter of interleukin (IL)-2 through promoting seven normal skin samples) and GSE31879 (including ten
Volume 2 Issue 1 (2023) 2 https://doi.org/10.36922/td.308