Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of General Surgery, Anqing First People's Hospital of Anhui Medical University, Anqing, China.
Front Immunol. 2024 Oct 9;15:1466286. doi: 10.3389/fimmu.2024.1466286. eCollection 2024.
As one of the malignant tumors with the highest incidence and fatality in the world, colon adenocarcinoma (COAD) has a very complex pathogenic mechanism, which has not yet been fully elucidated. Ubiquitin can regulate cell proliferation, cell cycle, apoptosis, DNA damage repair, and other processes by changing the activity of substrate proteins or causing ubiquitin-proteasome degradation. These are the key links in the pathogenesis of COAD, and ubiquitin plays an important role in the occurrence and development of COAD.
We integrated transcriptomics, single-cell and clinical omics, and TCGA and GEO databases of COAD patient data. Cox and Lasso regression was employed to assess ubiquitination genes in COAD for generating ubiquitination-related features. The aim was to evaluate the prognostic value of these features for tumors and their impact on the immune microenvironment. At the same time, the expression level of model genes was further analyzed using single-cell data. Finally, the expression and function of ASNS, a key gene for this trait, were detected .
In our study, based on identifiable changes in the expression of marker genes, this feature can be used to classify patients with COAD. Kaplan-Meier survival analysis indicated that those with elevated risk scores in each cohort experienced inferior outcomes. There is good validation in both the training queue and the validation queue. The results of the immune infiltration analysis showed that the immune infiltration rate was significantly increased in the high-risk group. After the knockdown of ASNS, an important gene in the signature, the activity and migration capacity of SW620 and RKO cell lines and colony formation capacity were dramatically reduced in cell tests.
We screened ubiquitination-related genes and constructed ubiquitination-related features, which can be used as reliable prognostic indicators of COAD. ASNS was identified as a possible biomarker for COAD.
结直肠癌（COAD）是世界上发病率和死亡率最高的恶性肿瘤之一，其发病机制非常复杂，尚未完全阐明。泛素可以通过改变底物蛋白的活性或引起泛素-蛋白酶体降解来调节细胞增殖、细胞周期、细胞凋亡、DNA 损伤修复等过程。这些都是 COAD 发病机制中的关键环节，泛素在 COAD 的发生发展中起着重要作用。
我们整合了 COAD 患者的转录组学、单细胞和临床组学以及 TCGA 和 GEO 数据库的数据。采用 Cox 和 Lasso 回归评估 COAD 中的泛素化基因，以生成泛素化相关特征。目的是评估这些特征对肿瘤的预后价值及其对免疫微环境的影响。同时，利用单细胞数据进一步分析模型基因的表达水平。最后，检测该特征关键基因 ASNS 的表达和功能。
在本研究中，基于标记基因表达的可识别变化，该特征可用于对 COAD 患者进行分类。Kaplan-Meier 生存分析表明，每个队列中风险评分升高的患者预后较差。在训练队列和验证队列中都得到了很好的验证。免疫浸润分析结果表明，高危组的免疫浸润率显著增加。在细胞试验中，敲低特征中重要基因 ASNS 后，SW620 和 RKO 细胞系的活性和迁移能力以及集落形成能力明显降低。
我们筛选了泛素化相关基因，并构建了泛素化相关特征，可作为 COAD 的可靠预后指标。ASNS 被鉴定为 COAD 的一个潜在生物标志物。
