关键词: Colon adenocarcinoma Homer protein homolog Immune cells Immune checkpoints Methylation MicroRNAs Prognostic

来  源:   DOI:10.1016/j.heliyon.2024.e33344   PDF(Pubmed)

Abstract:
UNASSIGNED: Homer protein homolog 3 (HOMER3), a factor implicated in both physiological and pathological processes, has been studied extensively to determine the relationship between its expression level and the prognosis of various malignancies. However, the significance and clinicopathological role of HOMER3 in colorectal adenocarcinoma remain unclear.
UNASSIGNED: In this study, bioinformatics techniques were used to find the correlation between high HOMER3 expression levels and clinicopathological features of colorectal adenocarcinoma (COAD) patients.
UNASSIGNED: Cellular experiments confirmed the differential expression of HOMER3 in tumor cells compared to normal cells. HOMER3 overexpression was significantly associated with COAD staging and carcinoembryonic antigen (CEA) levels. Patients with high HOMER3 expression levels have a poor prognosis. HOMER3 expression levels can be distinguished more accurately between tumor and non-tumor tissues (AUC = 0.634). The HOMER3 gene variation rate in COAD tissue was 0.7 %. Moreover, 16 of the 22 DNA methylation sites in HOMER3 were associated with COAD prognosis. Our findings confirmed that HOMER3 was positively correlated with immune cell infiltration and immune checkpoints (PD-1, CTLA-4, LMTK3, and LAG3) in COAD, Specifically, we will clearly state that while there is statistical significance, the actual strength of the correlations is weak. During KEGG enrichment analysis, HOMER3 was enriched along with DLG4 and SHANK1 in glutamatergic synapses. Additionally, upstream microRNAs that could bind to HOMER3 were predicted. These findings suggest that HOMER3 might be involved in COAD development and immune regulation.
UNASSIGNED: HOMER3 acts as a potential biomarker that can facilitate innovative developments in the diagnosis and prognostic assessment of COAD.
摘要:
荷马蛋白同源物3(HOMER3),一个涉及生理和病理过程的因素,已被广泛研究以确定其表达水平与各种恶性肿瘤预后之间的关系。然而,HOMER3在结直肠腺癌中的意义和临床病理作用尚不清楚.
在这项研究中,生物信息学技术用于发现高HOMER3表达水平与结直肠腺癌(COAD)患者临床病理特征之间的相关性。
细胞实验证实,与正常细胞相比,HOMER3在肿瘤细胞中的差异表达。HOMER3过表达与COAD分期和癌胚抗原(CEA)水平显着相关。具有高HOMER3表达水平的患者具有不良预后。HOMER3表达水平可以在肿瘤组织和非肿瘤组织之间更准确地区分(AUC=0.634)。COAD组织中HOMER3基因变异率为0.7%。此外,HOMER3中22个DNA甲基化位点中的16个与COAD预后相关。我们的研究结果证实,HOMER3与COAD中的免疫细胞浸润和免疫检查点(PD-1,CTLA-4,LMTK3和LAG3)呈正相关。具体来说,我们将明确指出,虽然有统计意义,相关性的实际强度较弱。在KEGG富集分析期间,HOMER3与DLG4和SHANK1一起在谷氨酸能突触中富集。此外,预测了可以与HOMER3结合的上游microRNA。这些发现表明,HOMER3可能参与COAD的发育和免疫调节。
HOMER3作为一种潜在的生物标志物,可以促进COAD诊断和预后评估的创新发展。
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