Dataset Information

TREM2 as a Potential Immune-Related Biomarker of Prognosis in Patients with Skin Cutaneous Melanoma Microenvironment.

ABSTRACT:

Background

The skin cutaneous melanoma (SKCM) is a devastating form of skin cancer triggered by genetic and environmental factors, and the incidence of SKCM has rapidly increased in recent years. Immune infiltration of the tumor microenvironment is positively associated with overall survival in many tumors. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily and a crucial signaling hub for multiple pathological pathways that mediate immunity. Although numerous evidences suggest a crucial role for TREM2 in tumorigenesis of some tumors, no systematic SKCM analysis of TREM2 is available. Mehods. The relationship between TREM2 expression and diagnostic and prognostic value of SKCM patients via using The Cancer Genome Atlas (TCGA) data. The expression level of TREM2 and clinical characteristic correlation in SKCM patients were assessed by the Wilcoxon rank sum test. The cox regression methods, Kaplan-Meier (KM), and log-rank test were used to assess the impact of TREM2 expression on the overall survival (OS). Furthermore, the Gene Set Enrichment Analysis (GSEA) and TIMER were performed to evaluate the enrichment pathways and potential functions and quantify the immune cell infiltration level for TREM2 expression.

Results

The TREM2 in SKCM sample expression levels was significantly higher than in normal tissues. Moreover, this expression level of TREM2 was also associated with the BMI of SKCM patients. KM overall survival analysis and OS curve displayed that a high-level TREM2 expression was significantly correlated with a better SKCM prognosis of patients as compared with a low level of TREM2 expression. The GSEA analysis also revealed that TREM2 was associated with immune functions, such as neutrophil activation.

Conclusion

TREM2 played a crucial role in SKCM, which might be a prognostic biomarker and correlated with immune infifiltrates in SKCM patients.

SUBMITTER: Zhu X

PROVIDER: S-EPMC9897921 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

TREM2 as a Potential Immune-Related Biomarker of Prognosis in Patients with Skin Cutaneous Melanoma Microenvironment.

Zhu Xinlin X Zeng Zhaoxiang Z Chen Min M Chen Xianzhen X Hu Dongying D Jiang Weiwei W Du Mingwei M Chen Tianyang T Chen Tiancheng T Liao Wanqing W Zhang Chao C Qu Ying Y Pan Weihua W

Disease markers 20230127

<h4>Background</h4>The skin cutaneous melanoma (SKCM) is a devastating form of skin cancer triggered by genetic and environmental factors, and the incidence of SKCM has rapidly increased in recent years. Immune infiltration of the tumor microenvironment is positively associated with overall survival in many tumors. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily and a crucial signaling hub for multiple pathological pathways t ...[more]

PMID: 36741909

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Project description:BackgroundSkin cutaneous melanoma is one of most aggressive type of cancers worldwide. Therefore, the identification of SKCM biomarkers is of great importance. FLG gene is one of the genes that encode proteins involved in epidermal formation. This was the first time to study the role of FLG in the prognosis and immune infiltrates of skin cutaneous melanoma.MethodsWe downloaded the somatic mutation data of 471 SKCM patients from the Cancer Genome Atlas (TCGA) database and analyzed the mutation profiles with "MafTools" package. The expression of FLG and the overall survival in SKCM were analyzed by GEPIA. Additionally, univariate and multivariate Cox analyses were used to compare several clinical features with survival rates. We used TIMER to investigate FLG expression and collection of immune infiltration levels in SKCM, as well as cumulative survival in SKCM. Meanwhile, we also used CIBERSORT to investigate the association between FLG and cancer immune infiltration. In addition, gene set enrichment analysis (GSEA) was performed using the TCGA dataset. Furthermore, data from GEO and HPA was used to validate the results.ResultsSingle nucleotide polymorphism (SNP) happened more frequently than insertion or deletion, and C > T was the most common of SNV in SKCM. We selected the first 15 mutated genes by analyzing 471 melanoma samples, and the prognosis analysis showed that only the high expression of mutated FLG gene was significantly correlated with the poor prognosis of SKCM. Multivariate Cox analysis showed that age, the worse tumor status, less lymph node metastasis, and FLG expression were independent factors for prognosis. Specifically, lower infiltration levels of B cell, CD8+ T cells, neutrophils, and dendritic cells correlated with poor survival outcomes in SKCM. GSEA revealed that FLG is closely related to cancer pathways and epidermal cell proliferation. In addition, the previous conclusions can be verified from external data from GEO and HPA.ConclusionThe discovery of mutant gene FLG as a biomarker of SKCM helps elucidate how changes in the immune environment promote the occurrence of cutaneous melanoma. Further analysis suggested that FLG might be a new predictor of SKCM prognosis.

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Dataset Information

TREM2 as a Potential Immune-Related Biomarker of Prognosis in Patients with Skin Cutaneous Melanoma Microenvironment.

Background

Results

Conclusion

Publications

TREM2 as a Potential Immune-Related Biomarker of Prognosis in Patients with Skin Cutaneous Melanoma Microenvironment.

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