Background and Objective: Lung cancer, the second most prevalent cancer globally, poses significant challenges in early detection and prognostic assessment. Despite advancements in targeted therapies and immunotherapy, the timely identification of relapse remains elusive. Blood-based liquid biopsy biomarkers, including circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating-free RNAs (cfRNAs), and extracellular vesicles (EVs)/exosomes, offer promise for non-invasive monitoring. Methods: We employ a comprehensive approach integrating miRNA/lncRNA/metabolomic datasets, following a mixed-methods content analysis, to identify candidate biomarkers in NSCLC. NSCLC-associated miRNA/gene/lncRNA associations were linked to in silico-derived molecular pathways. Results: For data validation, mass spectrometry-based untargeted metabolomics of plasma EVs highlighted miRNA/lncRNA/metabotypes, linking “glycerophospholipid metabolism” tolncRNA H19and “alanine, aspartate and glutamate metabolism” tomiR-29a-3p. Prognostic significance was established formiR-29a-3p, showing lower expression in NSCLC patients with disease progression compared to stable disease (p= 0.004). Kaplan–Meier survival analysis indicated that patients withmiR-29a-3punder-expression had significantly shorter overall survival (OS) (p= 0.038). Despite the expression oflncRNA H19in plasma EVs being undetected, its expression in plasma cfRNAs correlated significantly with disease progression (p= 0.035). Conclusions: Herein, we showcase the potential of plasma EV-derivedmiR-29a-3pas a prognostic biomarker and underscore the intricate interplay of miRNAs, lncRNAs, and metabolites in NSCLC biology. Our findings offer new insights and avenues for further exploration, contributing to the ongoing quest for effective biomarkers in early-stage NSCLC.
**背景与目的：** 肺癌是全球第二大常见癌症，其早期检测和预后评估面临重大挑战。尽管靶向治疗和免疫疗法取得了进展，但及时识别复发仍难以实现。基于血液的液体活检生物标志物，包括循环肿瘤细胞、游离DNA、循环肿瘤DNA、循环游离RNA以及细胞外囊泡/外泌体，为非侵入性监测提供了希望。 **方法：** 我们采用整合miRNA/lncRNA/代谢组学数据集并遵循混合方法内容分析的综合方法，以识别非小细胞肺癌中的候选生物标志物。将与非小细胞肺癌相关的miRNA/基因/lncRNA关联与通过计算机模拟推导的分子通路联系起来。 **结果：** 在数据验证方面，基于质谱的血浆细胞外囊泡非靶向代谢组学分析突出了miRNA/lncRNA/代谢表型，将"甘油磷脂代谢"与lncRNA H19、"丙氨酸、天冬氨酸和谷氨酸代谢"与miR-29a-3p联系起来。研究确立了miR-29a-3p的预后意义，与疾病稳定的患者相比，其在疾病进展的非小细胞肺癌患者中表达较低。Kaplan-Meier生存分析表明，miR-29a-3p低表达患者的总生存期显著缩短。尽管在血浆细胞外囊泡中未检测到lncRNA H19的表达，但其在血浆循环游离RNA中的表达与疾病进展显著相关。 **结论：** 本研究展示了血浆细胞外囊泡来源的miR-29a-3p作为预后生物标志物的潜力，并强调了miRNA、lncRNA和代谢物在非小细胞肺癌生物学中复杂的相互作用。我们的发现为早期非小细胞肺癌有效生物标志物的持续探索提供了新的见解和途径。
肿瘤(癌症)患者之家