Central Laboratory, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, China.
Department of Pathology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, China.
Aging (Albany NY). 2024 Feb 23;16(5):4378-4395. doi: 10.18632/aging.205594.
Lung adenocarcinoma (LUAD) is one of the most common malignant tumors worldwide. Small Ubiquitin-like Modifier (SUMO)-ylation plays a crucial role in tumorigenesis. However, the SUMOylation pathway landscape and its clinical implications in LUAD remain unclear. Here, we analyzed genes involved in the SUMOylation pathway in LUAD and constructed a SUMOylation pathway signature (SUMOPS) using the LASSO-Cox regression model, validated in independent cohorts. Our analysis revealed significant dysregulation of SUMOylation-related genes in LUAD, comprising of favorable or unfavorable prognostic factors. The SUMOPS model was associated with established molecular and histological subtypes of LUAD, highlighting its clinical relevance. The SUMOPS stratified LUAD patients into SUMOPS-high and SUMOPS-low subtypes with distinct survival outcomes and adjuvant chemotherapy responses. The SUMOPS-low subtype showed favorable responses to adjuvant chemotherapy. The correlations between SUMOPS scores and immune cell infiltration suggested that patients with the SUMOPS-high subtype exhibited favorable immune profiles for immune checkpoint inhibitor (ICI) treatment. Additionally, we identified UBA2 as a key SUMOylation-related gene with an increased expression and a poor prognosis in LUAD. Cell function experiment confirmed the role of UBA2 in promoting LUAD cell proliferation, invasion, and migration. These findings provide valuable insights into the SUMOylation pathway and its prognostic implications in LUAD, paving the way for personalized treatment strategies and the development of novel therapeutic targets.
肺腺癌（LUAD）是全球最常见的恶性肿瘤之一。小泛素样修饰物（SUMO）化在肿瘤发生中起着至关重要的作用。然而，LUAD 中 SUMOylation 途径的全景及其临床意义仍不清楚。在这里，我们分析了 LUAD 中参与 SUMOylation 途径的基因，并使用 LASSO-Cox 回归模型构建了 SUMOylation 途径特征（SUMOPS），并在独立队列中进行了验证。我们的分析揭示了 LUAD 中 SUMOylation 相关基因的显著失调，包括有利或不利的预后因素。SUMOPS 模型与 LUAD 的已建立的分子和组织学亚型相关联，突出了其临床相关性。SUMOPS 将 LUAD 患者分为 SUMOPS-高和 SUMOPS-低亚型，具有不同的生存结果和辅助化疗反应。SUMOPS-低亚型对辅助化疗有较好的反应。SUMOPS 评分与免疫细胞浸润的相关性表明，SUMOPS-高亚型的患者具有有利的免疫特征，适合免疫检查点抑制剂（ICI）治疗。此外，我们确定了 UBA2 作为一个关键的 SUMOylation 相关基因，在 LUAD 中表达增加且预后不良。细胞功能实验证实了 UBA2 在促进 LUAD 细胞增殖、侵袭和迁移中的作用。这些发现为 SUMOylation 途径及其在 LUAD 中的预后意义提供了有价值的见解，为个性化治疗策略和新的治疗靶点的开发铺平了道路。
