Long Noncoding RNA LINC02249 Is a Prognostic Biomarker and Correlates with Immunosuppressive Microenvironment in Skin Cutaneous Melanoma

Abstract

Skin cutaneous melanoma (SKCM) is one of the most aggressive and life-threatening tumors. It has a high incidence rate, as well as significant metastasis and fatality rates. To successfully treat SKCM and to increase the overall survival rate, early identification and risk stratification are both absolutely necessary. Long noncoding RNAs (lncRNAs) play a significant regulatory role in a variety of cancers. However, the expression and function of many lncRNAs have not been investigated. We evaluated the expression profile of the long noncoding RNA LINC02249 (LINC02249) in pan-cancers by using data on gene expression obtained from TCGA and GTEx. The biological function of LINC02249 was determined by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The prognostic value of LINC02249 expression in SKCM patients was statistically analyzed. Besides, the ssGSEA approach was utilized in order to investigate the degree to which LINC02249 expression is correlated with tumor immune infiltration. In this study, the expression of LINC02249 was found to be abnormally high in a variety of tumors, according to our findings. When compared with nontumor specimens, the level of expression of LINC02249 was shown to be significantly elevated in SKCM samples. GO and KEGG assays revealed LINC02249 may be involved in tumor progression. High expression of LINC02249 was associated with shorter overall survival and disease-specific survival of SKCM patients. More importantly, multivariate methods revealed that LINC02249 expression was an independent prognostic factor for SKCM cases. Using ssGSEA, we found that the expression of LINC02249 was negatively associated with different tumor-infiltrating immune cells, especially aDC, Treg, and macrophages. Overall, our findings suggested that LINC02249 can serve as a novel biomarker to predict the prognosis and immune infiltration in SKCM.

Regulatory miRNAs and lncRNAs in Skin Cancer: A Narrative Review

“…Similarly, long intergenic ncRNA 173 (LINC00173) expression was significantly higher in melanoma tissues compared to adjacent non-neoplastic tissues ( p < 0.01) and was expressed more frequently in melanoma patients with distant metastasis compared to patients at an earlier stage of melanoma [ 41 ]. Another study found that lncRNA LINC02249 expression was significantly elevated in cutaneous melanoma samples and a high expression of LINC02249 was associated with shorter overall survival in melanoma patients [ 42 ].…”

“…Squamous cell carcinoma (SCC) is the second most common non-melanoma skin ca cer. Local recurrence, regional metastases, distant metastases, and disease specific death occur at rates of 5, 5, 1, 1%, respectively [42]. Surgical excision is generally the standar treatment for low risk lesions.…”

The role of lncRNAs in the tumor microenvironment and immunotherapy of melanoma

“…At the same time, immune invasion analysis showed that HSD11B1-AS1 affected the activation of T cells, Th cells, dendritic cells and B cells ( 92 ). And the overexpression of lncRNA-LINC02249 is associated with a shorter survival time in melanoma patients, and affects the immune infiltration of dendritic cells, Treg cells and macrophages ( 93 ). LncRNA-SNHG16 regulates mitochondrial function, cell metabolism and the immune infiltration of Th cells and NK cells by competitively binding with let-7b-5p and targeting TUB4A ( 94 ).…”

Integration of single-cell and bulk RNA sequencing data reveals that CYTOR is a potential prognostic and immunotherapeutic response marker for skin cutaneous melanoma

“…Several lncRNAs have been shown to be differentially expressed in melanomas, and their expression has been shown to correlate with the metastasis and prognosis of melanomas 9 - 11 . Du et al 12 identified LINC02249 is a prognostic biomarker for cutaneous melanoma and associated with an immunosuppressive microenvironment. Zhang et al 13 analyzed the potential value of lncRNA-PRRT3-AS1 as a therapeutic target in SKCM.…”