Emergency Department, The Second Hospital of Dalian Medical University, Dalian, China.
Laboratory Animal Center, Dalian Medical University, Dalian, China.
PeerJ. 2024 Oct 29;12:e18406. doi: 10.7717/peerj.18406. eCollection 2024.
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.
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 using reverse transcription-quantitative polymerase chain reaction, western blotting, and immunohistochemistry (IHC).
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 conclusion, FOXD subfamily members (especially FOXD3) could serve as diagnostic and prognostic biomarkers for CRC and an immunotherapy target in patients with CRC.
叉头框（FOX）家族成员调节基因转录和表达。FOX 家族成员调节各种生物过程，如细胞增殖和肿瘤发生。FOXD 是 FOX 蛋白亚家族的一员，与多种癌症的预后不良有关。然而，FOXD 亚家族成员在结直肠癌（CRC）中的潜在临床价值尚未阐明。因此，在本研究中，我们旨在确定 FOXD 亚家族成员在 CRC 发展中的作用。
使用 HTSeq-count 数据、临床数据和单核苷酸多态性（来自癌症基因组图谱计划），并进行生物信息学分析（使用 DESEQ2 软件），我们鉴定了 CRC 中的差异表达基因（DEGs）。接下来，使用逆转录定量聚合酶链反应、western blot 和免疫组织化学（IHC）验证每个 DEG 的表达。
在 FOXD 亚家族成员中，FOXD3 的受试者工作特征曲线下面积为 0.949，表明 FOXD3 对 CRC 的总体诊断准确性较高。基因集富集分析表明，FOXD-DEGs 主要与细胞因子、细胞因子和细胞外基质受体相互作用等途径有关。Kaplan-Meier 曲线和列线图表明，FOXD1、FOXD3 和 FOXD4 具有预后意义。总之，FOXD 亚家族成员（尤其是 FOXD3）可作为 CRC 的诊断和预后生物标志物，并可作为 CRC 患者免疫治疗的靶点。
