Zhong Guanghui, Li Qing, Luo Yang, Liu Yufeng, Liu Dawei, Li Bin, Wang Tao
Department of Urology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong 510900, China.
J Oncol. 2022 Aug 25;2022:8943643. doi: 10.1155/2022/8943643. eCollection 2022.
Clear cell renal cell carcinoma (ccRCC) is, by far, the most prevalent and fatal kind of kidney cancer. Ferrochelatase (FECH) is an enzyme that performs a significant function in the onset and progression of many distinct kinds of malignant tumors. Nevertheless, its predictive usefulness in renal clear cell carcinoma (RCC) has not yet been fully investigated.
FECH expression in ccRCC and healthy adjoining tissues was primarily screened utilizing data sourced from The Cancer Genome Atlas (TCGA) and subsequently validated using data from an independent cohort derived from the Gene Expression Omnibus (GEO) and the Human Protein Atlas HPA databases. The relationship among FECH expression, clinicopathological parameters, and overall survival (OS) was assessed utilizing multivariate analysis and Kaplan-Meier survival curves. Additionally, the protein networks with FECH interaction were constructed with the aid of the online Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Gene ontology (GO) analysis, and gene set enrichment analysis (GSEA) were conducted based on TCGA data, and a single-sample GSEA was utilized to explore the link between FECH expression and the infiltration status of immune cells in the tumor. The Gene Expression Profiling Interactive Analysis (GEPIA) and TIMER databases were utilized to investigate the relationships of FECH expression with the infiltrating immune cells and the matching gene marker sets.
FECH expression was shown to be substantially lowered in ccRCC tumors as opposed to that observed in normal tissues ( < 0.05). Lower levels of FECH expression were shown to have a strong association with higher grades of cancer and more advanced TNM stages. The findings of multivariate and univariate analyses illustrated that the OS in patients with ccRCC with low FECH expression is shorter in contrast with that in the high FECH expression group ( < 0.05). It was discovered that CPOX and frataxin are key proteins that interact with FECH. ccRCC with FECH deficiency was linked to the lack of infiltrating immune cells and their respective marker sets, which included CD4+ T cells.
In ccRCC, decreased FECH expression was linked to disease progression, unfavorable prognosis, and impaired immune cell infiltration.
到目前为止，透明细胞肾细胞癌（ccRCC）是最常见且致命的肾癌类型。铁螯合酶（FECH）是一种在多种不同类型恶性肿瘤的发生和发展中发挥重要作用的酶。然而，其在肾透明细胞癌（RCC）中的预测效用尚未得到充分研究。
首先利用来自癌症基因组图谱（TCGA）的数据对ccRCC和健康相邻组织中的FECH表达进行初步筛选，随后使用来自基因表达综合数据库（GEO）和人类蛋白质图谱（HPA）数据库的独立队列数据进行验证。利用多变量分析和Kaplan-Meier生存曲线评估FECH表达、临床病理参数和总生存期（OS）之间的关系。此外，借助在线检索相互作用基因/蛋白质的搜索工具（STRING）构建与FECH相互作用的蛋白质网络。基于TCGA数据进行基因本体（GO）分析和基因集富集分析（GSEA），并利用单样本GSEA探索FECH表达与肿瘤中免疫细胞浸润状态之间的联系。利用基因表达谱交互分析（GEPIA）和TIMER数据库研究FECH表达与浸润免疫细胞及匹配基因标志物集之间的关系。
与正常组织相比，ccRCC肿瘤中FECH表达显著降低（<0.05）。较低水平的FECH表达与较高的癌症分级和更晚期的TNM分期密切相关。多变量和单变量分析结果表明，与FECH高表达组相比，FECH低表达的ccRCC患者的OS更短（<0.05）。发现CPOX和铁调素是与FECH相互作用的关键蛋白质。FECH缺陷的ccRCC与缺乏浸润免疫细胞及其各自的标志物集有关，其中包括CD4+T细胞。
在ccRCC中，FECH表达降低与疾病进展、不良预后和免疫细胞浸润受损有关。
