Gasparri Roberto, Papale Massimo, Sabalic Angela, Catalano Valeria, Deleonardis Annamaria, De Luca Federica, Ranieri Elena, Spaggiari Lorenzo
Department of Thoracic Surgery, European Institute of Oncology (IEO), IRCCS, 20141 Milan, Italy.
Unit of Clinical Pathology, Department of Laboratory Diagnostics, University Hospital "Policlinico Foggia", 71122 Foggia, Italy.
J Clin Med. 2024 Sep 29;13(19):5830. doi: 10.3390/jcm13195830.
Lung cancer (LC) is the leading cause of cancer-related deaths. Although low-dose computed tomography (LD-CT) reduces mortality, its clinical use is limited by cost, radiation, and false positives. Therefore, there is an urgent need for non-invasive and cost-effective biomarkers. The Raf Kinase Inhibitor Protein (RKIP) plays a crucial role in cancer development and progression and may also contribute to regulating the tumor-immune system axis. This protein has recently been described in biological fluids. Therefore, we conducted a pilot case-control study to assess RKIP and phosphorylated RKIP (pRKIP) levels in the urine and blood of LC patients. A novel enzyme linked immunosorbent assay (ELISA) assay was used to measure RKIP and pRKIP levels in urine and blood samples of two cohorts of LC patients and healthy controls (HSs). Furthermore, the biomarkers levels were correlated with tumor characteristics. Serum, but not urine, levels of RKIP were significantly elevated in LC patients, distinguishing them from low- and high-risk healthy subjects with 93% and 74% accuracy, respectively. The RKIP/pRKIP ratio (RpR score) showed an accuracy of 90% and 79% in distinguishing LC patients from HS and HR-HS, respectively. Additionally, the RpR score correlated better with dimension, stage, and lymph node involvement in the tumor group. The serum RKIP and pRKIP profile may be a promising novel biomarker for early-stage LC.
肺癌（LC）是癌症相关死亡的主要原因。尽管低剂量计算机断层扫描（LD-CT）可降低死亡率，但其临床应用受到成本、辐射和假阳性的限制。因此，迫切需要非侵入性且具有成本效益的生物标志物。Raf激酶抑制蛋白（RKIP）在癌症的发生和发展中起关键作用，也可能有助于调节肿瘤-免疫系统轴。这种蛋白最近已在生物体液中被描述。因此，我们进行了一项病例对照初步研究，以评估肺癌患者尿液和血液中的RKIP及磷酸化RKIP（pRKIP）水平。采用一种新型酶联免疫吸附测定（ELISA）法来检测两组肺癌患者和健康对照（HS）尿液和血液样本中的RKIP和pRKIP水平。此外，将这些生物标志物水平与肿瘤特征进行关联分析。肺癌患者血清中的RKIP水平显著升高，而尿液中则不然，分别以93%和74%的准确率将其与低风险和高风险健康受试者区分开来。RKIP/pRKIP比值（RpR评分）在区分肺癌患者与健康对照和高风险健康对照时，准确率分别为90%和79%。此外，RpR评分与肿瘤组的肿瘤大小、分期及淋巴结受累情况的相关性更好。血清RKIP和pRKIP谱可能是早期肺癌一种有前景的新型生物标志物。
