Wang Xiaoyan, Yu Pengcheng, Jia Wei, Wan Bingbing, Ling Zhougui, Tang Yangyang
Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.
Department of General Surgery, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, China.
Front Pharmacol. 2025 Jan 9;15:1539120. doi: 10.3389/fphar.2024.1539120. eCollection 2024.
Pancreatic cancer remains one of the deadliest malignancies, largely due to its late diagnosis and lack of effective therapeutic targets.
Using traditional machine learning methods, including random-effects meta-analysis and forward-search optimization, we developed a robust signature validated across 14 publicly available datasets, achieving a summary AUC of 0.99 in training datasets and 0.89 in external validation datasets. To further validate its clinical relevance, we analyzed 55 peripheral blood samples from pancreatic cancer patients and healthy controls using qPCR.
This study identifies and validates a novel five-gene transcriptomic signature (LAMC2, TSPAN1, MYO1E, MYOF, and SULF1) as both diagnostic biomarkers and potential drug targets for pancreatic cancer. The differential expression of these genes was confirmed, demonstrating their utility in distinguishing cancer from normal conditions with an AUC of 0.83. These findings establish the five-gene signature as a promising tool for both early, non-invasive diagnostics and the identification of actionable drug targets.
A five-gene signature is established robustly and has utility in diagnostics and therapeutic targeting. These findings lay a foundation for developing diagnostic tests and targeted therapies, potentially offering a pathway toward improved outcomes in pancreatic cancer management.
胰腺癌仍然是最致命的恶性肿瘤之一,主要原因是其诊断较晚且缺乏有效的治疗靶点。
我们使用包括随机效应荟萃分析和前向搜索优化在内的传统机器学习方法,开发了一种强大的特征标志物,并在14个公开可用的数据集中进行了验证,在训练数据集中的汇总曲线下面积(AUC)为0.99,在外部验证数据集中为0.89。为了进一步验证其临床相关性,我们使用定量聚合酶链反应(qPCR)分析了55份来自胰腺癌患者和健康对照的外周血样本。
本研究鉴定并验证了一种新的五基因转录组特征标志物(LAMC2、TSPAN1、MYO1E、MYOF和SULF1),其可作为胰腺癌的诊断生物标志物和潜在药物靶点。这些基因的差异表达得到了证实,其区分癌症与正常情况的AUC为0.83,证明了它们的实用性。这些发现确立了五基因特征标志物作为早期、非侵入性诊断以及识别可操作药物靶点的有前景工具。
一种五基因特征标志物得到了有力确立,在诊断和治疗靶向方面具有实用性。这些发现为开发诊断测试和靶向治疗奠定了基础,可能为改善胰腺癌管理的结果提供一条途径。