透明细胞肾细胞癌中 GFOD1 的表达及其在癌细胞增殖、迁移和侵袭中的作用

The goal of this research was to examine the expression levels of Glucose-Fructose Oxidoreductase Domain Containing 1 (GFOD1) and to explore how it influences the proliferation, migration, and invasion of cancer cells in clear cell renal cell carcinoma (ccRCC, also known as KIRC).

The Cancer Genome Atlas (TCGA) database was used to compare GFOD1 expression levels across various tumors, as well as differences in GFOD1 expression between individual tumors and their adjacent tissues. The expression of GFOD1 in bladder cancer, KIRC, renal chromophobe cell carcinoma, renal papillary carcinoma, and prostate cancer was evaluated using qRT-PCR and immunohistochemistry. The prognostic value of GFOD1 in KIRC patients from the TCGA database was analyzed using the Kaplan-Meier method. Differences in GFOD1 expression among various KIRC grades and stages were also compared. The transwell assay served to detect variations in the metastatic ability of cells and to uncover important factors in epithelial-mesenchymal transition (EMT). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of highly expressed genes was performed to explore the potential role of GFOD1 in ccRCC. In addition, the correlation between GFOD1 and cells of various immune subsets was evaluated to explore potential immunological pathways.

GFOD1 was significantly overexpressed in bladder cancer and KIRC. KIRC patients with elevated GFOD1 expression had better overall survival (OS) and disease-free survival (DFS) compared to those with lower expression levels (P < 0.05). In addition, GFOD1 expression was negatively correlated with tumor grade (P < 0.05). Knocking-down the expression of GFOD1 in KIRC cells enhanced the proliferation, migration, and invasion potential of the cells and promoted EMT. String protein interaction analysis showed that GFOD1 was significantly correlated with NKIRAS2, PHACTR1, HIVP1, HAO1, and other proteins. Pathway enrichment analysis of these genes indicated that GFOD1 was associated with multiple ion channel activation pathways, epithelial (epidermal) development, and extracellular matrix collagen function (P < 0.05). Furthermore, GFOD1 was associated with enrichment of natural killer cells and CD8 + T cells in tumor tissues.

GFOD1 may promote the proliferation, migration, and invasion of KIRC. Our findings may provide new prognostic biomarkers and potential therapeutic targets for KIRC patients.