Rosell Rafael, Santarpia Mariacarmela, Pedraz-Valdunciel Carlos, Ciappina Giuliana, Aguilar Andrés, Giménez-Capitán Ana, Ito Masaoki, González-Cao Maria, Molina-Vila Miguel Angel
Germans Trias i Pujol Health Sciences Institute and Hospital (IGTP), Badalona, Spain.
Catalan Institute of Oncology, Badalona, Spain.
J Liq Biopsy. 2023 Jul 27;1:100001. doi: 10.1016/j.jlb.2023.100001. eCollection 2023 Sep.
Lung cancer screening programs, particularly in the UK, have shown a decrease in lung cancer-related deaths among individuals who underwent low-dose computed tomography (CT) screening. Researchers are now focusing on evaluating cell-free DNA through various methods to determine if pre-diagnostic mutations can be detected years before clinical diagnosis. This could help identify individuals at high risk of developing lung cancer. However, while this approach has successfully identified precursors of follicular lymphoma, the presence of occult lung preneoplasia in non-small-cell lung cancer still requires further investigation. The TRACERx consortium is conducting extensive research to comprehensively assess the detection and progression of non-small cell lung cancers (NSCLC). Liquid biopsy is being used in advanced stages of the disease to monitor disease progression, predict treatment response, and identify targetable driver oncogenic mutations and fusion genes. Intense research is also underway to identify numerous diagnostic gene signatures with high accuracy for early-stage lung cancer. However, a more focused clinical approach is needed, with a mechanistic focus on the key pathways of cancer development. Loss of liver kinase B1 () function and deactivation due to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of tobacco-specific carcinogens, could potentially be traced and contribute to the development of new biomarkers. This testing could complement machine-learning approaches. The discovery of epidermal growth factor receptor () and Kirsten rat sarcoma viral oncogene homolog () mutations in healthy lung tissues by TRACERx investigators may also lead to the development of novel diagnostic tools. Tumor protein 53 () loss should also be considered as a marker that could contribute to malignant transformation. Intercepting aggressive non-small-cell lung cancer is a pressing priority. In this review, we discuss our experience and explore other research on exosomes and plasma circular RNA as potential biomarkers. Circular RNAs, formed through non-sequential back-splicing of pre-mRNA transcripts, play a role in epithelial-mesenchymal transition, with many of them regulated by the RNA-binding protein Quaking. Platelet RNA has shown promise in detecting early and late-stage cancer. The extensive exploration of liquid biopsy aims to provide affordable methods for tracing circulating precursors of non-small-cell lung cancer, highlighting the importance of its mission.
肺癌筛查项目，尤其是在英国，已显示在接受低剂量计算机断层扫描（CT）筛查的个体中，与肺癌相关的死亡人数有所减少。研究人员目前正专注于通过各种方法评估游离DNA，以确定是否能在临床诊断前数年检测到诊断前突变。这有助于识别患肺癌风险高的个体。然而，虽然这种方法已成功识别出滤泡性淋巴瘤的前体，但非小细胞肺癌中隐匿性肺前病变的存在仍需进一步研究。TRACERx联盟正在进行广泛研究，以全面评估非小细胞肺癌（NSCLC）的检测和进展情况。液体活检正用于疾病的晚期阶段，以监测疾病进展、预测治疗反应，并识别可靶向的驱动致癌突变和融合基因。目前也正在进行深入研究，以识别大量用于早期肺癌的高精度诊断基因特征。然而，需要一种更有针对性的临床方法，从机制上关注癌症发展的关键途径。肝激酶B1（）功能的丧失以及因烟草特异性致癌物的代谢产物4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁醇（NNAL）导致的失活，可能可以被追踪到，并有助于开发新的生物标志物。这种检测可以补充机器学习方法。TRACERx研究人员在健康肺组织中发现表皮生长因子受体（）和 Kirsten 大鼠肉瘤病毒癌基因同源物（）突变，这也可能导致新型诊断工具的开发。肿瘤蛋白53（）的缺失也应被视为可能促成恶性转化的一个标志物。拦截侵袭性非小细胞肺癌是当务之急。在这篇综述中，我们讨论我们的经验，并探索关于外泌体和血浆环状RNA作为潜在生物标志物的其他研究。环状RNA是通过前体mRNA转录本的非顺序反向剪接形成的，在上皮-间质转化中起作用，其中许多受RNA结合蛋白颤抖蛋白调节。血小板RNA在检测早期和晚期癌症方面已显示出前景。对液体活检的广泛探索旨在提供经济实惠的方法来追踪非小细胞肺癌的循环前体，凸显了其使命的重要性。
