Bai Changsen, Hao Qianhui, Chen Yunxiang, Wang Jiayi, Xiao Jiawei, Kang Da Hyun, Ren Li
Department of Clinical Laboratory, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon, Korea.
Transl Lung Cancer Res. 2025 Jun 30;14(6):2239-2256. doi: 10.21037/tlcr-2025-530. Epub 2025 Jun 18.
Lung cancer remains one of the leading causes of cancer-related deaths worldwide. Early detection is crucial for improving prognosis and survival rates. This study aimed to identify the low-abundance plasma proteins as potential diagnostic biomarkers for early-stage non-small cell lung cancer (NSCLC) and to distinguish malignant from benign lung nodules.
Using a sodium-type Y zeolite-polymer polyanionic complex (NaY-PPC)-based low-abundance proteomics, we analyzed 181 plasma samples from healthy controls (HC; n=65), patients with benign lung nodules (BNs; n=21), and patients with early-stage NSCLC (n=95). Principal component analysis (PCA) and heatmap visualization were employed for differential analysis. The diagnostic performance of candidate biomarkers was evaluated using receiver operating characteristic (ROC) curves, and enzyme-linked immunosorbent assay (ELISA) was used for validation. Functional studies, including fructose-bisphosphate aldolase C (ALDOC) knockdown, were conducted to assess the role of ALDOC in NSCLC progression.
We identified 23 significantly differentially expressed proteins, with ALDOC showing the most promising diagnostic potential. ALDOC could effectively distinguish NSCLC patients from HCs [area under the curve (AUC) =0.994] and from those with BNs (AUC =0.720). Combining ALDOC with the traditional biomarkers carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin fragment 21-1 (CYFRA21-1) improved the differentiation between NSCLC and BN (AUC =0.824). ELISA validation confirmed the findings from the proteomics analysis. Additionally, ALDOC was upregulated in NSCLC tissues, and its high expression correlated with poor overall survival. Knockdown of ALDOC significantly reduced NSCLC cell growth and motility, suggesting its tumor-promoting role.
ALDOC is a promising diagnostic biomarker for early-stage NSCLC, with potential clinical utility in distinguishing malignant lung nodules from BNs. This study highlights the value of low-abundance proteomics in identifying novel biomarkers for lung cancer detection and risk assessment.
肺癌仍然是全球癌症相关死亡的主要原因之一。早期检测对于改善预后和生存率至关重要。本研究旨在鉴定低丰度血浆蛋白作为早期非小细胞肺癌（NSCLC）的潜在诊断生物标志物，并区分恶性和良性肺结节。
使用基于钠型Y沸石-聚合物聚阴离子复合物（NaY-PPC）的低丰度蛋白质组学，我们分析了来自健康对照（HC；n = 65）、良性肺结节患者（BN；n = 21）和早期NSCLC患者（n = 95）的181份血浆样本。采用主成分分析（PCA）和热图可视化进行差异分析。使用受试者工作特征（ROC）曲线评估候选生物标志物的诊断性能，并使用酶联免疫吸附测定（ELISA）进行验证。进行了包括果糖-1,6-二磷酸醛缩酶C（ALDOC）敲低在内的功能研究以评估ALDOC在NSCLC进展中的作用。
我们鉴定出23种显著差异表达的蛋白质，其中ALDOC显示出最有前景的诊断潜力。ALDOC能够有效地区分NSCLC患者与HC（曲线下面积[AUC] = 0.994）以及与BN患者（AUC = 0.720）。将ALDOC与传统生物标志物癌胚抗原（CEA）、神经元特异性烯醇化酶（NSE）和细胞角蛋白片段21-1（CYFRA21-1）相结合可改善NSCLC与BN之间的区分（AUC = 0.824）。ELISA验证证实了蛋白质组学分析的结果。此外，ALDOC在NSCLC组织中上调，其高表达与总体生存率差相关。敲低ALDOC显著降低NSCLC细胞的生长和运动能力，表明其具有促肿瘤作用。
ALDOC是早期NSCLC的一种有前景的诊断生物标志物，在区分恶性肺结节与BN方面具有潜在的临床应用价值。本研究突出了低丰度蛋白质组学在鉴定用于肺癌检测和风险评估的新型生物标志物方面的价值。
