SKAP2作为一种新的HNSCC预后生物标志物：遗传和功能验证

IF 2.5 4区综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES

Journal of Radiation Research and Applied Sciences Pub Date : 2025-08-19 DOI:10.1016/j.jrras.2025.101884

Jiao Lei , Xuexian Yao , Li Nie , Yuyang Li , Dong Wang

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引用次数: 0

摘要

目的：该研究首次确定SKAP2作为头颈部鳞状细胞癌（HNSCC）的预后生物标志物。方法对基因表达综合数据库（Gene Expression Omnibus， GEO）中237例nsscc相关数据进行分析。差异表达基因分析（DEG）、加权基因共表达网络分析（WGCNA）和机器学习（LASSO/SVM-RFE/RF）——通过优先排序具有高预测能力的基因来改进DEG/WGCNA输出——应用于基因筛选，然后通过孟德尔随机化进行因果验证。进行生存分析，并基于TCGA-HNSC队列数据（n = 566）构建SKAP2预后模型。通过SKAP2敲低HNSCC细胞系（FaDu/SCC-15）进行功能验证，评估增殖（CCK-8）、迁移（Transwell）和凋亡（流式细胞术）。结果通过DEGs分析和WGCNA，研究人员确定了153个与HNSCC相关的重叠基因。三种机器学习算法随后确定了与HNSCC进展密切相关的三个关键疾病相关基因。孟德尔随机化（MR）分析显示SKAP2是一个特别显著的致病基因（OR = 1.307; 95% CI = 1.023-1.669; P = 0.032）。TCGA数据库的临床数据显示，SKAP2表达升高的HNSCC患者的生存结果明显较差（P = 0.018）。多因素Cox回归分析确定SKAP2为独立的预后指标（HR = 1.283; 95% CI = 1.009-1.632; P = 0.042）。体外实验证实，SKAP2敲低显著抑制FaDu和SCC-15细胞增殖（P < 0.001）和迁移（P < 0.0001），促进细胞凋亡（P < 0.0001）。结论skap2有望成为HNSCC的临床重要生物标志物和治疗靶点，但需要前瞻性试验来验证其临床应用价值。它通过增殖和迁移途径调节肿瘤的进展。

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SKAP2 as a novel prognostic biomarker in HNSCC: Genetic and functional validation

Objective

This first-of-its-kind study identifies SKAP2 as a causal prognostic biomarker in head and neck squamous cell carcinoma (HNSCC).

Methods

HNSCC-related datasets from the Gene Expression Omnibus (GEO) database (n = 237) were analyzed. Differential expression genes analysis (DEGs), weighted gene co-expression network analysis (WGCNA), and machine learning (LASSO/SVM-RFE/RF) - refining DEG/WGCNA outputs by prioritizing genes with high predictive power - were applied for gene screening, followed by Mendelian randomization for causal verification. Survival analysis was performed, and a SKAP2 prognostic model was constructed on the basis of TCGA-HNSC cohort data (n = 566). Functional validation was performed via SKAP2 knockdown in HNSCC cell lines (FaDu/SCC-15), assessing proliferation (CCK-8), migration (Transwell), and apoptosis (flow cytometry).

Results

Through DEGs analysis and WGCNA, researchers identified 153 overlapping genes critically involved in HNSCC. Three machine learning algorithms subsequently pinpointed three key disease-associated genes strongly linked to HNSCC progression. Mendelian randomization (MR) analysis revealed SKAP2 as a particularly significant causal gene (OR = 1.307; 95 % CI = 1.023–1.669; P = 0.032). Clinical data from the TCGA database demonstrated that HNSCC patients exhibiting elevated SKAP2 expression faced markedly worse survival outcomes (P = 0.018). Multivariate Cox regression analysis established SKAP2 as an independent prognostic marker (HR = 1.283; 95 % CI = 1.009–1.632; P = 0.042). In vitro experiments confirmed that SKAP2 knockdown significantly inhibited FaDu and SCC-15 cell proliferation (P < 0.001) and migration (P < 0.0001) and promoted apoptosis (P < 0.0001).

Conclusion

SKAP2 shows promise as a clinically significant biomarker and therapeutic target in HNSCC, though prospective trials are needed to validate clinical utility. It regulates tumor progression through proliferation and migration pathways.

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来源期刊

Journal of Radiation Research and Applied Sciences MULTIDISCIPLINARY SCIENCES-

自引率

5.90%

发文量

130

审稿时长

16 weeks

期刊介绍： Journal of Radiation Research and Applied Sciences provides a high quality medium for the publication of substantial, original and scientific and technological papers on the development and applications of nuclear, radiation and isotopes in biology, medicine, drugs, biochemistry, microbiology, agriculture, entomology, food technology, chemistry, physics, solid states, engineering, environmental and applied sciences.