Huang Mao, Ming Liang, Jiang Hongbo, Jiang Ping, Jiang Xi, Yin Haofan, Hong Honghai
Department of Clinical Laboratory, Zhuhai People's Hospital (Zhuhai Hospital affiliated with Jinan University), Zhuhai, Guangdong, China.
Department of Clinical Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
J Cancer. 2023 Jul 16;14(12):2198-2208. doi: 10.7150/jca.85681. eCollection 2023.
Non-small cell lung cancer (NSCLC) was a disease with poor outcomes, partly because there were no high-efficiency non-invasive diagnostic biomarkers. The RNA modification status of 5-Methylcytosine (mC) has been shown to be a biomarker for various diseases, but its potentiality to be a diagnostic biomarker for NSCLC remained inconclusive. In this research, we collected peripheral leukocyte samples from 141 patients with NSCLC and 90 normal people as controls to evaluate the extent of mC RNA modification. We found that the mC modification levels in leukocytes of NSCLC patients were decreased dramatically, which were compared to the normal controls, and levels of mC modification decreased progressively with tumor stage. Importantly, mC modification exhibited superior diagnostic value compared to carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), cytokeratin 19 fragment (Cyfra21-1), and carbohydrate antigen 125 (CA125), which demonstrated area under the curves (AUCs) of 0.912, 0.773, 0.669, 0.754, and 0.732, respectively. The combination of mC modification with these serum tumor biomarkers further improved the AUC to 0.960. A nomogram model incorporating mC modification also provided an effectively diagnostic tool for NSCLC. Collectively, our findings suggested that mC modification in leukocytes held promise as a prospective biomarker for NSCLC diagnosis.
非小细胞肺癌（NSCLC）是一种预后较差的疾病，部分原因是缺乏高效的非侵入性诊断生物标志物。5-甲基胞嘧啶（mC）的RNA修饰状态已被证明是多种疾病的生物标志物，但其作为NSCLC诊断生物标志物的潜力仍不明确。在本研究中，我们收集了141例NSCLC患者的外周血白细胞样本和90例正常人作为对照，以评估mC RNA修饰程度。我们发现，与正常对照组相比，NSCLC患者白细胞中的mC修饰水平显著降低，且mC修饰水平随肿瘤分期逐渐降低。重要的是，与癌胚抗原（CEA）、鳞状细胞癌抗原（SCC）、细胞角蛋白19片段（Cyfra21-1）和糖类抗原125（CA125）相比，mC修饰表现出更高的诊断价值，其曲线下面积（AUC）分别为0.912、0.773、0.669、0.754和0.732。mC修饰与这些血清肿瘤生物标志物的联合使用进一步将AUC提高到0.960。纳入mC修饰的列线图模型也为NSCLC提供了一种有效的诊断工具。总体而言，我们的研究结果表明，白细胞中的mC修饰有望成为NSCLC诊断的前瞻性生物标志物。
