Wu Shaobo, Liang Yuxia, Zang Qijuan, Xing Zixuan, Yin Pan, Sun Ruifang, Dai Bingling
Health Science Center, Xi'an Jiaotong University, Shaanxi, Xi'an 710061, China.
Department of Imaging, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, Xi'an 710061, China.
Appl Bionics Biomech. 2022 May 14;2022:5160748. doi: 10.1155/2022/5160748. eCollection 2022.
Skin 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.
We 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.
Single 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.
The 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.
皮肤黑色素瘤是全球最具侵袭性的癌症类型之一。因此，鉴定皮肤黑色素瘤（SKCM）生物标志物至关重要。丝聚合蛋白（FLG）基因是编码参与表皮形成蛋白质的基因之一。这是首次研究FLG在皮肤黑色素瘤预后和免疫浸润中的作用。
我们从癌症基因组图谱（TCGA）数据库下载了471例SKCM患者的体细胞突变数据，并使用“MafTools”软件包分析突变谱。通过GEPIA分析SKCM中FLG的表达和总生存期。此外，单因素和多因素Cox分析用于比较几种临床特征与生存率。我们使用TIMER研究SKCM中FLG表达与免疫浸润水平的关系以及SKCM的累积生存率。同时，我们还使用CIBERSORT研究FLG与癌症免疫浸润之间的关联。此外，使用TCGA数据集进行基因集富集分析（GSEA）。此外，来自GEO和HPA的数据用于验证结果。
单核苷酸多态性（SNP）比插入或缺失更频繁发生，C>T是SKCM中最常见的单核苷酸变异（SNV）。通过分析471个黑色素瘤样本，我们选择了前15个突变基因，预后分析表明只有突变的FLG基因高表达与SKCM的不良预后显著相关。多因素Cox分析表明，年龄、较差的肿瘤状态、较少的淋巴结转移和FLG表达是预后的独立因素。具体而言，B细胞、CD8+T细胞、中性粒细胞和树突状细胞的浸润水平较低与SKCM的不良生存结果相关。GSEA显示FLG与癌症通路和表皮细胞增殖密切相关。此外，先前的结论可以从来自GEO和HPA的外部数据中得到验证。
突变基因FLG作为SKCM生物标志物的发现有助于阐明免疫环境变化如何促进皮肤黑色素瘤的发生。进一步分析表明，FLG可能是SKCM预后的新预测指标。
