Chen Xiawu, Huang Chengqing, Liao Yingping, Chen Xiaoxun
Department of Gastrointestinal Surgery, Guigang City People's Hospital, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang, 537100, Guangxi, China.
Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530000, Guangxi, China.
Discov Oncol. 2025 Aug 2;16(1):1459. doi: 10.1007/s12672-025-03331-3.
Colorectal cancer (CRC) is a global health burden because of its high mortalities. It is crucial to discover new biomarkers that can help predict the outcome of patients as well as identify new therapeutic targets to improve treatment options for CRC patients. EGLN1, a protein belonging to the family of prolyl hydroxylase domain-containing proteins, has been associated with the progression of various cancer types. However, its involvement in CRC remains uncertain.
We conducted an analysis of EGLN1 expression levels in colorectal cancer (CRC) tissues using publicly available datasets. EGLN1 expression was also evaluated in relation to patient survival. To explore the potential biological functions and signaling pathways associated with EGLN, we performed gene set enrichment analysis (GSEA). We also investigated the immune landscape of EGLN1 in CRC by examining its association with immune infiltration and immune-related markers.
We consistently observed a significant decrease in EGLN1 level in CRC tumor tissues when compared to normal tissues, indicating its potential role as a tumor suppressor gene specific to CRC. The diagnostic potential of EGLN1 was substantiated by its effective discrimination between normal and tumor tissues in patients with CRC. Functional enrichment analysis further uncovered EGLN1's involvement in the regulation of crucial biological processes, cellular components, and molecular functions relevant to CRC development and progression. The correlation analysis revealed the potential immunomodulatory role of EGLN1, affecting immune checkpoint molecules, antigen presentation, and immune cell trafficking within the tumor microenvironment. Additionally, high level of EGLN1 exhibited a significant association with improved recurrence-free survival (RFS) and emerged as an independent prognostic factor. Knockdown experiments demonstrated EGLN1's role in suppressing cell proliferation and migration in CRC.
In summary, our findings position EGLN1 as a promising multi-faceted biomarker in CRC, with implications for prognosis, immune microenvironment modulation, and potential therapeutic targeting.
由于结直肠癌（CRC）的高死亡率，它成为了一个全球性的健康负担。发现能够帮助预测患者预后的新生物标志物以及识别新的治疗靶点以改善CRC患者的治疗选择至关重要。EGLN1是一种属于含脯氨酰羟化酶结构域蛋白家族的蛋白质，它与多种癌症类型的进展有关。然而，其在CRC中的作用仍不明确。
我们使用公开可用的数据集对结直肠癌（CRC）组织中的EGLN1表达水平进行了分析。还评估了EGLN1表达与患者生存的关系。为了探索与EGLN相关的潜在生物学功能和信号通路，我们进行了基因集富集分析（GSEA）。我们还通过检查其与免疫浸润和免疫相关标志物的关联，研究了CRC中EGLN1的免疫格局。
与正常组织相比，我们始终观察到CRC肿瘤组织中EGLN1水平显著降低，表明其作为CRC特异性肿瘤抑制基因的潜在作用。EGLN1在CRC患者中区分正常组织和肿瘤组织的有效能力证实了其诊断潜力。功能富集分析进一步揭示了EGLN1参与了与CRC发生和进展相关的关键生物学过程、细胞成分和分子功能的调节。相关性分析揭示了EGLN1的潜在免疫调节作用，影响肿瘤微环境中的免疫检查点分子、抗原呈递和免疫细胞运输。此外，高水平的EGLN1与无复发生存期（RFS）改善显著相关，并成为一个独立的预后因素。敲低实验证明了EGLN1在抑制CRC细胞增殖和迁移中的作用。
总之，我们的研究结果表明EGLN1是CRC中有前景的多方面生物标志物，对预后、免疫微环境调节和潜在治疗靶点具有重要意义。
