Necroptosis-related LncRNAs in skin cutaneous melanoma: evaluating prognosis, predicting immunity, and guiding therapy

Abstract Background An increasing amount of research has speculated that necroptosis could be a therapeutic strategy for treating cancer. However, understanding the prognostic value of the necroptosis-related long non-coding RNAs (NRLs) in skin cutaneous melanoma (SKCM, hereafter referred to as melanoma) remains poor and needs to be developed. Our research aims to construct a model based on NRLs for the prognosis of patients with melanoma. Methods We obtained the RNA-seq and clinical data from The Cancer Genome Atlas (TCGA) database and retrieved 86 necroptosis-related genes from the GeneCards database. The lncRNAs associated with necroptosis were identified via the Pearson correlation coefficient, and the prognostic model of melanoma was constructed using LASSO regression. Next, we employed multiple approaches to verify the accuracy of the model. Melanoma patients were categorized into two groups (high-risk and low-risk) according to the results of LASSO regression. The relationships between the risk score and survival status, clinicopathological correlation, functional enrichment, immune infiltration, somatic mutation, and drug sensitivity were further investigated. Finally, the functions of AL162457.2 on melanoma proliferation, invasion, and migration were validated by in vitro experiments. Results The prognostic model consists of seven NRLs (EBLN3P, AC093010.2, LINC01871, IRF2-DT, AL162457.2, AC242842.1, HLA-DQB1-AS1) and shows high diagnostic efficiency. Overall survival in the high-risk group was significantly lower than in the low-risk group, and risk scores could be used to predict melanoma survival outcomes independently. Significant differences were evident between risk groups regarding the expression of immune checkpoint genes, immune infiltration, immunotherapeutic response and drug sensitivity analysis. A series of functional cell assays indicated that silencing AL162457.2 significantly inhibited cell proliferation, invasion, and migration in A375 cells. Conclusion Our prognostic model can independently predict the survival of melanoma patients while providing a basis for the subsequent investigation of necroptosis in melanoma and a new perspective on the clinical diagnosis and treatment of melanoma

Liquid-liquid phase separation throws novel insights into treatment strategies for skin cutaneous melanoma

Abstract Background In recent years, there has been growing evidence indicating a relationship between liquid–liquid phase separation (LLPS) and cancer development. However, to date, the clinical significance of LLPS in skin cutaneous melanoma (SKCM, hereafter referred to as melanoma) remains to be elucidated. In the current study, the impact of LLPS-related genes on melanoma prognosis has been explored. Methods LLPS-related genes were retrieved from the DrLLPS database. The prognostic feature for LLPS in melanoma was developed in The Cancer Genome Atlas (TCGA) dataset and verified in the GSE65904 cohort. Based on risk scores, melanoma patients were categorized into high- and low-risk groups. Thereafter, the differences in clinicopathological correlation, functional enrichment, immune landscape, tumor mutational burden, and impact of immunotherapy between the two groups were investigated. Finally, the role of key gene TROAP in melanoma was validated by in vitro and in vivo experiments. Results The LLPS-related gene signature was developed based on MLKL, PARVA, PKP1, PSME1, RNF114, and TROAP. The risk score was a crucial independent prognostic factor for melanoma and patients with high-risk scores were related to a worse prognosis. Approximately, all immune-relevant characteristics, such as immune cell infiltration and immune scores, were extremely evident in patients with low-risk scores. The findings from the in vitro and in vivo experiments indicated that the viability, proliferation, and invasion ability of melanoma cells were drastically decreased after the knockdown of TROAP. Conclusion Our gene signature can independently predict the survival of melanoma patients. It provides a basis for the exploration of the relationship between LLPS and melanoma and can offer a fresh perspective on the clinical diagnosis and treatment of the disease

Immune Landscape and an RBM38-Associated Immune Prognostic Model with Laboratory Verification in Malignant Melanoma

Background: Current studies have revealed that RNA-binding protein RBM38 is closely related to tumor development, while its role in malignant melanoma remains unclear. Therefore, this research aimed to investigate the function of RBM38 in melanoma and the prognosis of the disease. Methods: Functional experiments (CCK-8 assay, cell colony formation, transwell cell migration/invasion experiment, wound healing assay, nude mouse tumor formation, and immunohistochemical analysis) were applied to evaluate the role of RBM38 in malignant melanoma. Immune-associated differentially expressed genes (DEGs) on RBM38 related immune pathways were comprehensively analyzed based on RNA sequencing results. Results: We found that high expression of RBM38 promoted melanoma cell proliferation, invasion, and migration, and RBM38 was associated with immune infiltration. Then, a five-gene (A2M, NAMPT, LIF, EBI3, and ERAP1) model of RBM38-associated immune DEGs was constructed and validated. Our signature showed superior prognosis capacity compared with other melanoma prognostic signatures. Moreover, the risk score of our signature was connected with the infiltration of immune cells, immune-regulatory proteins, and immunophenoscore in melanoma. Conclusions: We constructed an immune prognosis model using RBM38-related immune DEGs that may help evaluate melanoma patient prognosis and immunotherapy modalities