Forkhead box D subfamily genes in colorectal cancer: potential biomarkers and therapeutic targets

结直肠癌中的叉头框 D 亚家族基因:潜在的生物标志物和治疗靶点

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作者:Ying Chen #, Haiyan Qiao #, Ruiqi Zhong, Lei Sun, Bingbing Shang

Background

The forkhead box (FOX) family members regulate gene transcription and expression. FOX family members regulate various biological processes, such as cell proliferation and tumorigenesis. FOXD, a FOX protein subfamily, is associated with poor prognosis for various cancers. However, the potential clinical value of FOXD subfamily members in colorectal cancer (CRC) has not yet been elucidated. Therefore, in this study, we aimed to determine the role of the FOXD subfamily members in CRC development.

Methods

Using HTSeq-count data, clinical data, and single-nucleotide polymorphisms (obtained from The Cancer Genome Atlas Project), and bioinformatics analyses (using DESEQ2 software), we identified differentially expressed genes (DEGs) in CRC. Next, each DEG expression was validated in vitro using reverse transcription-quantitative polymerase chain reaction, western blotting, and immunohistochemistry (IHC).

Results

Among the FOXD subfamily members, the area under the receiver operating characteristic curve of FOXD3 was 0.949, indicating that FOXD3 has a high overall diagnostic accuracy for CRC. Gene Set Enrichment Analysis revealed that FOXD-DEGs were mainly related to pathways such as cytokine, cytokine, and extracellular matrix receptor interactions. Kaplan-Meier curves and nomograms showed that FOXD1, FOXD3, and FOXD4 were prognostically significant. In

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