Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, Jilin, China.
Department of Plastic Surgery, China Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China.
Sci Rep. 2022 Nov 28;12(1):20460. doi: 10.1038/s41598-022-24353-9.
Skin cutaneous melanoma (SKCM) is the most lethal form of skin cancers owing to high invasiveness and high metastatic potential. Tumor microenvironment (TME) provides powerful evidences for discerning SKCM, raising the prospect to identify biomarkers of SKCM. Based on the transcriptome profiles of patients with SKCM and the corresponding clinical information from The Cancer Genome Atlas (TCGA), we used ESTIMATE algorithm to calculate ImmuneScore and StromalScore and identified the TME-Related differentially expressed genes (DEGs), than the intersected TME-Related DEGs were used for subsequent functional enrichment analysis. Protein-protein interaction (PPI) analysis was used to identify the functionality-related DEGs and univariate Cox regression analysis was used to identify the survival-related DEGs. Furthermore, SKCM-related DEGs were identified based on two Gene Expression Omnibus (GEO) datasets. Finally, we intersected functionality-related DEGs, survival-related DEGs, and SKCM-related DEGs, ascertaining that six DEGs (CCL4, CXCL10, CCL5, GZMB, C1QA, and C1QB) function as core TME-related genes (CTRGs). Significant differences of GZMB, C1QA, and C1QB expressions were found in gender and clinicopathologic staging of SKCM. High levels of GZMB, C1QA, and C1QB expressions were associated with favorable prognosis. Gene set enrichment analysis (GSEA) showed that cell-cell interaction, cell behavior, and intracellular signaling transduction may be mainly involved in both C1QA, C1QB and GZMB expressions and metabolism of phospholipid and amino acid, transcription, and translation may be implicated in low GZMB expressions. C1QA, C1QB, and GZMB are novel SKCM-relating CTRGs, providing promising immune-related prognostic biomarkers for SKCM.
皮肤皮肤黑色素瘤(SKCM)是最致命的皮肤癌形式,由于其高度侵袭性和高转移性潜力。肿瘤微环境(TME)为辨别 SKCM 提供了有力的证据,提出了识别 SKCM 生物标志物的前景。基于 SKCM 患者的转录组谱和来自癌症基因组图谱(TCGA)的相应临床信息,我们使用 ESTIMATE 算法计算免疫评分和基质评分,并确定了与 TME 相关的差异表达基因(DEGs),然后将交集的与 TME 相关的 DEGs 用于后续的功能富集分析。蛋白质-蛋白质相互作用(PPI)分析用于识别功能相关的 DEGs,单变量 Cox 回归分析用于识别与生存相关的 DEGs。此外,还基于两个基因表达综合数据库(GEO)数据集识别了 SKCM 相关的 DEGs。最后,我们交集了功能相关的 DEGs、与生存相关的 DEGs 和 SKCM 相关的 DEGs,确定了六个 DEGs(CCL4、CXCL10、CCL5、GZMB、C1QA 和 C1QB)作为核心肿瘤微环境相关基因(CTRGs)。在 SKCM 的性别和临床病理分期中发现 GZMB、C1QA 和 C1QB 表达存在显著差异。GZMB、C1QA 和 C1QB 高表达与预后良好相关。基因集富集分析(GSEA)表明,细胞-细胞相互作用、细胞行为和细胞内信号转导可能主要涉及 C1QA、C1QB 和 GZMB 的表达以及磷脂和氨基酸代谢、转录和翻译可能涉及 GZMB 的低表达。C1QA、C1QB 和 GZMB 是新型 SKCM 相关的 CTRGs,为 SKCM 提供了有前途的免疫相关预后生物标志物。