Widjaja Lomanto Markus Yovian, Wanandi Septelia Inawati, Jayusman Achmad Mulawarman, Lukmanto Donny, Prayitno Yuniar Harris, Sutandyo Noorwati
Master's Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
J Liq Biopsy. 2025 Mar 9;8:100291. doi: 10.1016/j.jlb.2025.100291. eCollection 2025 Jun.
Previous studies found that cigarette smoke (CS) exposure could induce NSCLC malignancy and miRNA dysregulation. Yet, the association of CS-induced miRNA dysregulation and NSCLC malignancy has not been clearly understood. This study aimed to evaluate the effect of CS exposure in smokers on the expression of miR-10b-5p and miR-320b in extracellular vesicles (EVs) from NSCLC patients.
Bioinformatic analysis was conducted to validate miRNA candidates. Blood and tissue samples were collected from NSCLC patients (n = 21) with smoking and non-smoking history. EVs were isolated from plasma and miRNAs were extracted from the isolated EVs. The miRNAs relative expression was analyzed and compared.
In silico analysis identified miR-320b and miR-10b-5p as potential biomarkers for diagnosing NSCLC in smokers. Experimental analysis revealed differential expression of EVs-associated miRNAs in NSCLC patients with smoking and non-smoking histories. EVs-associated miR-10b-5p was significantly overexpressed in smoker NSCLC patients (p = 0.000), while miR-320b expression was significantly lower in this group (p = 0.018). Additionally, smoking intensity influenced miRNA expression, with higher smoking intensity correlating with increased miR-10b-5p expression and decreased miR-320b expression. ROC analysis demonstrated that EVs were a superior source of miRNAs compared to plasma for NSCLC diagnostics. miR-10b-5p and miR-320b in EVs showed higher diagnostic performance (AUC 0.878; 0.739) compared to plasma (AUC 0.628; 0.559).
CS exposure induces different expression of miR-10b-5p and miR-320b in EVs of NSCLC patients with smoking history. EV-related miR-10b-5p and miR-320b showed potential to be utilized as prognostic biomarker for smokers NSCLC patients.
先前的研究发现，接触香烟烟雾（CS）可诱发非小细胞肺癌（NSCLC）恶变和微小RNA（miRNA）失调。然而，CS诱导的miRNA失调与NSCLC恶变之间的关联尚未完全明确。本研究旨在评估CS暴露对NSCLC患者细胞外囊泡（EV）中miR-10b-5p和miR-320b表达的影响。
进行生物信息学分析以验证候选miRNA。收集有吸烟和无吸烟史的NSCLC患者（n = 21）的血液和组织样本。从血浆中分离出EV，并从分离出的EV中提取miRNA。分析并比较miRNA的相对表达。
计算机分析确定miR-320b和miR-10b-5p为诊断吸烟患者NSCLC的潜在生物标志物。实验分析显示，有吸烟和无吸烟史的NSCLC患者中，与EV相关的miRNA表达存在差异。与EV相关的miR-10b-5p在吸烟的NSCLC患者中显著过表达（p = 0.000），而该组中miR-320b表达显著降低（p = 0.018）。此外，吸烟强度影响miRNA表达，吸烟强度越高，miR-10b-5p表达增加，miR-320b表达降低。ROC分析表明，与血浆相比，EV是NSCLC诊断中miRNA的更好来源。与血浆（AUC 0.628；0.559）相比，EV中的miR-10b-5p和miR-320b显示出更高的诊断性能（AUC 0.878；0.739）。
CS暴露导致有吸烟史的NSCLC患者EV中miR-10b-5p和miR-320b表达不同。与EV相关的miR-10b-5p和miR-320b有潜力用作吸烟的NSCLC患者的预后生物标志物。
