Table 5_Comprehensive circRNA profiling of platelets and exosomes identifies hsa_circ_0061274 as a novel biomarker for lung adenocarcinoma.xlsx

BackgroundLung adenocarcinoma (LUAD) is usually detected late; sensitive, minimally invasive early-detection tools are urgently needed. Circular RNAs (circRNAs) in liquid biopsies are promising cancer biomarkers, yet it remains unclear which blood component—platelets or plasma exosomes—offers the richest and most informative circRNA source.
Materials and methodsHigh-throughput RNA sequencing was performed on platelets and plasma exosomes collected from LUAD patients and age-matched healthy donors. Differential circRNAs expression was analyzed after stringent quality filtering and normalization. A candidate reference gene was selected by stability testing (geNorm, NormFinder); diagnostic performance of the top LUAD-associated circRNA was validated in independent cohorts encompassing healthy controls and patients with benign pulmonary nodules; ROC curves were generated and AUCs calculated.
ResultsPlatelets contained 15–20-fold more distinct circRNAs than plasma exosomes. hsa_circ_0001380 was identified as a stably expressed reference suitable for platelet circRNA quantification. hsa_circ_0061274 was significantly down-regulated in LUAD platelets (log2FC ≈ −1.8, FDR < 0.01). In validation cohorts, hsa_circ_0061274 discriminated LUAD from healthy controls with an AUC of 0.85 (95% CI 0.79–0.91), from benign pulmonary nodules with an AUC of 0.75 (95% CI 0.68–0.82), and stage I LUAD with an Area Under the Curve (AUC) of 0.68 (95% CI 0.60–0.76). Platelet-derived circRNAs thus provide robust, minimally invasive biomarkers for early LUAD detection and pulmonary nodule characterization.

肺腺癌（Lung adenocarcinoma, LUAD）通常于晚期确诊，临床亟需灵敏且微创的早期检测手段。液体活检中的环状RNA（circRNAs）是极具潜力的癌症生物标志物，但目前仍未明确何种血液组分——血小板抑或血浆外泌体——可提供丰度最高、信息最丰富的环状RNA来源。

材料与方法：本研究对肺腺癌患者与年龄匹配的健康供体采集的血小板及血浆外泌体开展高通量RNA测序。经严格质量过滤与归一化处理后，分析差异表达的环状RNA。通过稳定性分析（geNorm、NormFinder）筛选候选内参基因；在包含健康对照与肺良性结节患者的独立队列中，验证与肺腺癌相关的Top环状RNA的诊断效能；绘制受试者工作特征（Receiver Operating Characteristic, ROC）曲线并计算曲线下面积（AUC）。

结果：血小板中含有的独特环状RNA数量较血浆外泌体高15~20倍。hsa_circ_0001380被鉴定为适用于血小板环状RNA定量的稳定表达内参基因。hsa_circ_0061274在肺腺癌患者血小板中显著下调（log₂FC≈-1.8，错误发现率（False Discovery Rate, FDR）<0.01）。在验证队列中，hsa_circ_0061274区分肺腺癌与健康对照的AUC为0.85（95%置信区间：0.79~0.91），区分肺腺癌与肺良性结节的AUC为0.75（95%置信区间：0.68~0.82），区分I期肺腺癌的AUC为0.68（95%置信区间：0.60~0.76）。综上，血小板来源的环状RNA可为肺腺癌早期检测及肺结节定性提供稳定可靠的微创生物标志物。