Zhang Yanqiu, Li Yaling, Yan Hongwei
Department of Dermatology, The First Hospital of China Medical University, Shenyang, 110001, People's Republic of China.
Clin Cosmet Investig Dermatol. 2023 Feb 21;16:463-477. doi: 10.2147/CCID.S395854. eCollection 2023.
Melanoma is a highly malignant skin tumor with a poor prognosis. Identification of novel biomarkers might potentially reveal the underlying mechanisms of melanoma progression.
We demonstrated the relationship between pan-cancer expression and melanoma samples in The Cancer Genome Atlas (TCGA) database. Next, the Kaplan-Meier plot and Cox regression analysis determined the prognostic value of in melanoma. Biological pathway enrichment was screened by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), enabling the correlation analysis between the immune infiltration level and expression in melanoma. Our final claim was validated using qPCR, immunohistochemistry, Western blot, cell colony formation assays, ethynyldeoxyuridine (Edu) analysis, and cell Invasion assays.
Our study revealed that the high expression correlates with poor overall survival of melanoma patients. Moreover, a low expression of was found in the A375 cell line. In addition, has significant prognostic value in melanoma diagnosis, with an AUC of 0.896. Prognostic analysis showed the low expression of to be independently associated with melanoma patients. Moreover, the expression of was significantly correlated with B cells, eosinophils, macrophages, neutrophils, NK cells, T helper cells, Tregs, Th1 cells, Th17 cells, and Th2 cells. PCR and immunohistochemistry indicated to be significantly downregulated in melanoma. The cell colony formation assay showed knockout increased the proliferation of A375 cells.
Our study established low levels of to be poor prognostic markers, enabling immunosuppressive cell infiltration in melanoma.
黑色素瘤是一种预后较差的高度恶性皮肤肿瘤。鉴定新的生物标志物可能有助于揭示黑色素瘤进展的潜在机制。
我们在癌症基因组图谱(TCGA)数据库中展示了泛癌表达与黑色素瘤样本之间的关系。接下来,通过Kaplan-Meier曲线和Cox回归分析确定了其在黑色素瘤中的预后价值。通过基因本体论(GO)、京都基因与基因组百科全书(KEGG)和基因集富集分析(GSEA)筛选生物通路富集情况,从而进行黑色素瘤中免疫浸润水平与表达之间的相关性分析。我们的最终结论通过定量聚合酶链反应(qPCR)、免疫组织化学、蛋白质免疫印迹法、细胞集落形成试验、乙炔基脱氧尿苷(Edu)分析和细胞侵袭试验进行了验证。
我们的研究表明,高表达与黑色素瘤患者较差的总生存期相关。此外,在A375细胞系中发现低表达。此外,在黑色素瘤诊断中具有显著的预后价值,曲线下面积(AUC)为0.896。预后分析表明,低表达与黑色素瘤患者独立相关。此外,的表达与B细胞、嗜酸性粒细胞、巨噬细胞、中性粒细胞、自然杀伤细胞、辅助性T细胞、调节性T细胞、Th1细胞、Th17细胞和Th2细胞显著相关。PCR和免疫组织化学表明在黑色素瘤中显著下调。细胞集落形成试验表明敲除可增加A375细胞的增殖。
我们的研究确定低水平是不良预后标志物,可导致黑色素瘤中免疫抑制细胞浸润。