Prognostic significance of APOBEC1 and its role in lung squamous cell carcinoma: insights from chromatin regulator-based modeling and experimental validation.

IF 2.8 3区医学 Q2 ONCOLOGY

Expert Review of Anticancer Therapy Pub Date : 2025-08-09 DOI:10.1080/14737140.2025.2544869

Min Liang, Chaohao Zhang, Shengming Liu

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引用次数: 0

Abstract

Introduction: Chromatin regulators (CRs) are critical in cancer development, yet their prognostic value in lung squamous cell carcinoma (LUSC) remains unclear. This study aimed to develop a CR-based prognostic model and explore the role of APOBEC1 in LUSC progression.

Methods: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed. Gene Ontology and KEGG pathway enrichment were performed. Prognostic CRs were identified using univariate Cox and Lasso analyses. Drug sensitivity was assessed via the Drug Signatures Database. Key CRs were validated by PCR. APOBEC1 expression and prognosis were evaluated through pan-cancer analysis and experimentally validated in LUSC cell lines using colony formation, CCK-8, wound healing, and transwell assays.

Results: An eight-gene CR-based signature was established, achieving 5-year AUCs of 0.87, 0.92, and 0.73 in the TCGA training, validation, and GEO datasets, respectively. High-risk patients showed enrichment in cancer-related pathways, greater immune infiltration, and elevated immune checkpoint expression. They were also more sensitive to Dasatinib, Bexarotene, and Bicalutamide. APOBEC1 was overexpressed across multiple cancer types and promoted proliferation and migration in LUSC cell lines.

Conclusions: This study presents a robust CR-based survival model and highlights APOBEC1 as a potential therapeutic target in LUSC.

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APOBEC1的预后意义及其在肺鳞状细胞癌中的作用：基于染色质调控因子的建模和实验验证的见解

简介：染色质调节因子（CRs）在癌症发展中至关重要，但其在肺鳞状细胞癌（LUSC）中的预后价值尚不清楚。本研究旨在建立基于cr的预后模型，并探讨APOBEC1在LUSC进展中的作用。方法：分析肿瘤基因组图谱（TCGA）和基因表达图谱（GEO）的转录组学和临床数据。进行基因本体和KEGG通路富集。使用单变量Cox和Lasso分析确定预后cr。通过药物特征数据库评估药物敏感性。用PCR方法验证关键基因。通过泛癌分析评估APOBEC1的表达和预后，并通过菌落形成、CCK-8、伤口愈合和transwell试验在LUSC细胞系中进行实验验证。结果：建立了基于8个基因的cr特征，TCGA训练、验证和GEO数据集的5年auc分别为0.87、0.92和0.73。高危患者表现出肿瘤相关通路的富集、免疫浸润的增强和免疫检查点表达的升高。他们对达沙替尼、贝沙罗汀和比卡鲁胺也更敏感。APOBEC1在多种癌症类型中过表达，并促进LUSC细胞系的增殖和迁移。结论：这项研究提出了一个强大的基于cr的生存模型，并强调APOBEC1是LUSC的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Anticancer Therapy 医学-肿瘤学

CiteScore

5.10

自引率

3.00%

发文量

100

审稿时长

4-8 weeks

期刊介绍： Expert Review of Anticancer Therapy (ISSN 1473-7140) provides expert appraisal and commentary on the major trends in cancer care and highlights the performance of new therapeutic and diagnostic approaches. Coverage includes tumor management, novel medicines, anticancer agents and chemotherapy, biological therapy, cancer vaccines, therapeutic indications, biomarkers and diagnostics, and treatment guidelines. All articles are subject to rigorous peer-review, and the journal makes an essential contribution to decision-making in cancer care. Comprehensive coverage in each review is complemented by the unique Expert Review format and includes the following sections: Expert Opinion - a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results Article Highlights – an executive summary of the author’s most critical points.