Background: Despite extensive endeavors to establish cell-free circulating biomarkers for lung cancer diagnosis, clinical adoption remains elusive. Noteworthy, emergent evidence suggests the pivotal roles of red blood cells (RBCs) and their derivatives in tumorigenesis, illuminating potential avenues for diagnostic advancements using blood cell-derived microRNAs (miRNAs). Methods: We executed microarray analyses on three principal blood cell types—RBCs, peripheral blood mononuclear cells (PBMCs), and neutrophils—encompassing 26 lung cancer patients and 26 healthy controls. Validation was performed using droplet digital PCR within an additional cohort comprising 42 lung cancer and 39 control cases. Results: Our investigation unearthed distinct miRNA profiles associated with lung cancer across all examined blood cell types. Intriguingly, RBC-miRNAs emerged as potential novel biomarkers for lung cancer, an observation yet to be documented. Importantly, integrating miRNAs from disparate blood cell types yielded a superior diagnostic accuracy for lung cancer over individual cell-type miRNAs. Subsequently, we formulated three diagnostic panels, adeptly discerning non-small cell lung cancer, adenocarcinoma, and squamous cell carcinoma, maintaining consistency across various disease stages. Conclusion: RBC-derived molecules introduce novel cancer biomarkers, and exploiting miRNA profiles across varied blood cell types unveils a promising frontier for lung cancer’s early detection and histological classification.
背景:尽管已投入大量努力建立用于肺癌诊断的无细胞循环生物标志物,但其临床应用仍面临挑战。值得注意的是,新出现的证据表明红细胞及其衍生物在肿瘤发生中具有关键作用,这为利用血细胞来源的微RNA(miRNA)进行诊断提供了潜在的新途径。方法:我们对26例肺癌患者和26例健康对照者的三种主要血细胞类型——红细胞、外周血单个核细胞和中性粒细胞——进行了微阵列分析,并在包含42例肺癌和39例对照病例的独立队列中使用微滴式数字PCR进行了验证。结果:研究发现所有检测的血细胞类型均存在与肺癌相关的独特miRNA谱。值得注意的是,红细胞miRNA可能成为肺癌的新型生物标志物,这一发现尚未见报道。重要的是,整合不同血细胞类型的miRNA比单一细胞类型的miRNA具有更高的肺癌诊断准确性。随后,我们构建了三个诊断组合,能够有效区分非小细胞肺癌、腺癌和鳞状细胞癌,并在不同疾病阶段保持一致性。结论:红细胞来源的分子为癌症生物标志物研究提供了新方向,利用不同血细胞类型的miRNA谱为肺癌的早期检测和组织学分型开辟了前景广阔的新领域。
MicroRNA Profiling of Red Blood Cells for Lung Cancer Diagnosis