Coexpressed Genes That Promote the Infiltration of M2 Macrophages in Melanoma Can Evaluate the Prognosis and Immunotherapy Outcome

Abstract

Purpose. To improve immunotherapy efficacy for melanoma, a coexpression network and key genes of M2 macrophages in melanoma were explored. A prognostic risk assessment model was established for M2-related coexpressed genes, and the role of M2 macrophages in the immune microenvironment of melanoma was elucidated. Method. We obtained mRNA data from melanoma and peritumor tissue samples from The Cancer Genome Atlas-skin cutaneous melanoma (TCGA-SKCM). Then, we used CIBERSORT to calculate the proportion of M2 macrophage cells. A coexpression module most related to M2 macrophages in TCGA-SKCM was determined by analyzing the weighted gene coexpression network, and a coexpression network was established. After survival analysis, factors with significant results were incorporated into a Cox regression analysis to establish a model. The model’s essential genes were analyzed using functional enrichment, GSEA, and subgroup and total carcinoma. Finally, external datasets GSE65904 and GSE78220 were used to verify the prognostic risk model. Results. The yellow-green module was the coexpression module most related to M2 macrophages in TCGA-SKCM; NOTCH3, DBN1, KDELC2, and STAB1 were identified as the essential genes that promoted the infiltration of M2 macrophages in melanoma. These genes are concentrated in antigen treatment and presentation, chemokine, cytokine, the T cell receptor pathway, and the IFN-γ pathway. These factors were analyzed for survival, and factors with significant results were included in a Cox regression analysis. According to the methods, a model related to M2-TAM coexpressed gene was established, and the formula was risk score = 0.25 ∗ NOTCH 3 + 0.008 ∗ DBN 1 − 0.031 ∗ KDELC 2 − 0.032 ∗ STAB 1 . The new model was used to perform subgroup evaluation and external queue validation. The results showed good prognostic ability. Conclusion. We proposed a Cox proportional hazards regression model associated with coexpression genes of melanoma M2 macrophages that may provide a measurement method for generating prognosis scores in patients with melanoma. Four genes coexpressed with M2 macrophages were associated with high levels of infiltration of M2 macrophages. Our findings may provide significant candidate biomarkers for the treatment and monitoring of melanoma.

Development and Validation of a CD8+ T Cell Infiltration-Related Signature for Melanoma Patients

“…However, the specific mechanism of how these genes influence T cell function remains elusive, it would be very interesting to further investigate into each of them in the following study. In this work, we found the combination of these six genes had a novel and good predictivity on melanoma patients, which performed better than the existing signature genes (Supplementary Figures 4, 5) (43,44,(49)(50)(51). Although the six gene signature in our work had a similar performance with the signature from Tian' s study for melanoma patients' survival, our signature had a better capability in predicting patients' response to immunotherapy (Figures 7H, K, Supplementary Figures 7A-C).…”

“…We further compared the predictiblibity of this signature with other previously developed immune-related signatures. Eleven studies were screened out after literature searching (42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52), but five signatures were not included for further analyses for at least one of the following reasons: lack of formula to calculate the risk score or immune-related score; lack of validation in extra datasets; lack of RNA expression data of some signature genes in validated datasets in the current work (45)(46)(47)(48)52). As reflected by the AUC values at 1-year, 3-year and 5-years in Supplementary Figures 4A-D and 5A-C, the signatures developed in our work and Tian's work had relatively better performance in predicting outcome of melanoma patients.…”

Synthesize Analysis of the IFN-γ and Immune Infiltrates of m6A RNA Methylation Regulators in Human Skin Cutaneous Melanoma

“…In contrast, the expression of were positively correlated with six immune cell in ltrations Activated CD4.T.cellna, CD8.T.cellna and Immature.B.cellna. Yan K, et al proposed a Cox proportional hazards regression model of melanoma M2 macrophages for generating prognosis score in patients [39]. On that basis, CD8 + T cell-related factors and the co-expression network in melanoma.…”

Lung Adenocarcinoma Cells Promote Self-Migration and Self-Invasion by Activating Neutrophils to Upregulate Notch3 Expression of Cancer Cells

“…In gastric cancer, the expression of Notch3 is correlated with the infiltration of immune cells, including CD8 + T cells, Tregs, and M2 macrophages ( Cui et al, 2020 ). According to Yan et al, Notch3 expression is closely related to the infiltration of M2 macrophage in melanoma tissues ( Yan et al, 2021 ). Although the aforementioned evidence suggests an interaction between Notch3 and immune cells, how Notch3 interacts with immune cells, particularly TANs in lung cancer, remained unexplored.…”